2-230185999-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_080424.4(SP110):c.1274T>C(p.Leu425Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.872 in 1,613,516 control chromosomes in the GnomAD database, including 614,159 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.87 ( 57874 hom., cov: 31)

Exomes 𝑓: 0.87 ( 556285 hom. )

Consequence

SP110
NM_080424.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts U:1B:6

Conservation

PhyloP100: -0.354

Publications

58 publications found

Variant links:

Genes affected

SP110 (HGNC:5401): (SP110 nuclear body protein) The nuclear body is a multiprotein complex that may have a role in the regulation of gene transcription. This gene is a member of the SP100/SP140 family of nuclear body proteins and encodes a leukocyte-specific nuclear body component. The protein can function as an activator of gene transcription and may serve as a nuclear hormone receptor coactivator. In addition, it has been suggested that the protein may play a role in ribosome biogenesis and in the induction of myeloid cell differentiation. Alternative splicing has been observed for this gene and three transcript variants, encoding distinct isoforms, have been identified. [provided by RefSeq, Jul 2008]

SP110 links:

SP140 (HGNC:17133): (SP140 nuclear body protein) This gene encodes a member of the SP100 family of proteins, which are share common domains including an N-terminal homogeneously staining region domain followed by a SP100/autoimmune regulator/NucP41/P75/deformed epidermal autoregulatory factor domain, a plant homeobox zinc finger, and a bromodomain. The encoded protein is interferon-inducible and is expressed at high levels in the nuclei of leukocytes. Variants of this gene have been associated with multiple sclerosis, Crohn's disease, and chronic lymphocytic leukemia. Alternative splicing results in multiple variants. [provided by RefSeq, Aug 2016]

SP140 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.0717378E-6).

BP6

Variant 2-230185999-A-G is Benign according to our data. Variant chr2-230185999-A-G is described in ClinVar as Benign. ClinVar VariationId is 5539.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SP110	NM_080424.4 link	c.1274T>C	p.Leu425Ser	missense_variant	Exon 11 of 19	ENST00000258381.11	NP_536349.3	Q9HB58-6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SP110	ENST00000258381.11 link	c.1274T>C	p.Leu425Ser	missense_variant	Exon 11 of 19	2	NM_080424.4	ENSP00000258381.6		Q9HB58-6

Frequencies

GnomAD3 genomes

AF:

0.872

AC:

132580

AN:

152068

Hom.:

57849

Cov.:

show subpopulations

Gnomad AFR

AF:

0.851

Gnomad AMI

AF:

0.878

Gnomad AMR

AF:

0.892

Gnomad ASJ

AF:

0.900

Gnomad EAS

AF:

0.997

Gnomad SAS

AF:

0.923

Gnomad FIN

AF:

0.862

Gnomad MID

AF:

0.889

Gnomad NFE

AF:

0.867

Gnomad OTH

AF:

0.866

GnomAD2 exomes

AF:

0.890

AC:

223707

AN:

251476

AF XY:

0.889

show subpopulations

Gnomad AFR exome

AF:

0.851

Gnomad AMR exome

AF:

0.923

Gnomad ASJ exome

AF:

0.900

Gnomad EAS exome

AF:

0.998

Gnomad FIN exome

AF:

0.862

Gnomad NFE exome

AF:

0.865

Gnomad OTH exome

AF:

0.881

GnomAD4 exome

AF:

0.872

AC:

1274205

AN:

1461330

Hom.:

556285

Cov.:

AF XY:

0.873

AC XY:

634789

AN XY:

726990

show subpopulations

African (AFR)

AF:

0.847

AC:

28354

AN:

33466

American (AMR)

AF:

0.922

AC:

41218

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.904

AC:

23631

AN:

26134

East Asian (EAS)

AF:

0.999

AC:

39661

AN:

39698

South Asian (SAS)

AF:

0.917

AC:

79085

AN:

86248

European-Finnish (FIN)

AF:

0.858

AC:

45838

AN:

53418

Middle Eastern (MID)

AF:

0.873

AC:

5036

AN:

5768

European-Non Finnish (NFE)

AF:

0.862

AC:

958498

AN:

1111498

Other (OTH)

AF:

0.876

AC:

52884

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

8670

17340

26010

34680

43350

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21234

42468

63702

84936

106170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.872

AC:

132661

AN:

152186

Hom.:

57874

Cov.:

AF XY:

0.874

AC XY:

65007

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.850

AC:

35281

AN:

41496

American (AMR)

AF:

0.892

AC:

13649

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.900

AC:

3120

AN:

3466

East Asian (EAS)

AF:

0.997

AC:

5166

AN:

5180

South Asian (SAS)

AF:

0.922

AC:

4443

AN:

4818

European-Finnish (FIN)

AF:

0.862

AC:

9145

AN:

10606

Middle Eastern (MID)

AF:

0.881

AC:

259

AN:

294

European-Non Finnish (NFE)

AF:

0.867

AC:

58967

AN:

68002

Other (OTH)

AF:

0.866

AC:

1830

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

863

1727

2590

3454

4317

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

898

1796

2694

3592

4490

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.836

Hom.:

137874

Bravo

AF:

0.873

TwinsUK

AF:

0.857

AC:

3176

ALSPAC

AF:

0.864

AC:

3330

ESP6500AA

AF:

0.846

AC:

3729

ESP6500EA

AF:

0.871

AC:

7491

ExAC

AF:

0.887

AC:

107679

Asia WGS

AF:

0.942

AC:

3275

AN:

3478

EpiCase

AF:

0.870

EpiControl

AF:

0.866

ClinVar

Significance: Benign

Submissions summary: Uncertain:1Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Dec 03, 2021

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 98% of patients studied by a panel of primary immunodeficiencies. Number of patients: 93. Only high quality variants are reported. -

Hepatic veno-occlusive disease-immunodeficiency syndrome

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mycobacterium tuberculosis, susceptibility to

Uncertain:1

Apr 01, 2007

OMIM

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:literature only

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.55

CADD

Benign

0.28

(source)

DANN

Benign

0.27

DEOGEN2

Benign

0.0016

.;T;T;.;.

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.00029

LIST_S2

Benign

0.10

T;T;T;T;T

MetaRNN

Benign

0.0000011

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.20

N;N;.;N;.

PhyloP100

-0.35

PrimateAI

Benign

0.21

PROVEAN

Benign

0.88

N;N;N;N;N

REVEL

Benign

0.035

Sift

Benign

0.82

T;T;T;T;T

Sift4G

Benign

0.53

T;T;T;T;T

Polyphen

0.0

B;B;B;.;.

Vest4

0.054

MPC

0.19

ClinPred

0.0023

GERP RS

-1.8

Varity_R

0.025

gMVP

0.041

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over