2-230213010-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.334T>C(p.Trp112Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.891 in 1,613,738 control chromosomes in the GnomAD database, including 641,644 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 0.92 ( 64041 hom., cov: 30)

Exomes 𝑓: 0.89 ( 577603 hom. )

Consequence

SP110
NM_080424.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.189

Publications

33 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=8.1801585E-7).

BP6

Variant 2-230213010-A-G is Benign according to our data. Variant chr2-230213010-A-G is described in ClinVar as Benign. ClinVar VariationId is 403465.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.334T>C	p.Trp112Arg	missense_variant	Exon 4 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.334T>C	p.Trp112Arg	missense_variant	Exon 4 of 19	2	NM_080424.4	ENSP00000258381.6		Q9HB58-6

Frequencies

GnomAD3 genomes

AF:

0.917

AC:

139312

AN:

152002

Hom.:

63987

Cov.:

show subpopulations

Gnomad AFR

AF:

0.978

Gnomad AMI

AF:

0.879

Gnomad AMR

AF:

0.918

Gnomad ASJ

AF:

0.924

Gnomad EAS

AF:

0.997

Gnomad SAS

AF:

0.943

Gnomad FIN

AF:

0.867

Gnomad MID

AF:

0.927

Gnomad NFE

AF:

0.879

Gnomad OTH

AF:

0.914

GnomAD2 exomes

AF:

0.910

AC:

226551

AN:

248960

AF XY:

0.909

show subpopulations

Gnomad AFR exome

AF:

0.981

Gnomad AMR exome

AF:

0.936

Gnomad ASJ exome

AF:

0.925

Gnomad EAS exome

AF:

0.998

Gnomad FIN exome

AF:

0.868

Gnomad NFE exome

AF:

0.877

Gnomad OTH exome

AF:

0.897

GnomAD4 exome

AF:

0.888

AC:

1298374

AN:

1461618

Hom.:

577603

Cov.:

AF XY:

0.890

AC XY:

646874

AN XY:

727134

show subpopulations

African (AFR)

AF:

0.982

AC:

32867

AN:

33480

American (AMR)

AF:

0.935

AC:

41824

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.928

AC:

24246

AN:

26134

East Asian (EAS)

AF:

0.999

AC:

39649

AN:

39700

South Asian (SAS)

AF:

0.937

AC:

80856

AN:

86256

European-Finnish (FIN)

AF:

0.865

AC:

46167

AN:

53388

Middle Eastern (MID)

AF:

0.914

AC:

5273

AN:

5766

European-Non Finnish (NFE)

AF:

0.875

AC:

973199

AN:

1111782

Other (OTH)

AF:

0.899

AC:

54293

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

7890

15781

23671

31562

39452

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21330

42660

63990

85320

106650

<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:

0.917

AC:

139425

AN:

152120

Hom.:

64041

Cov.:

AF XY:

0.917

AC XY:

68175

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.978

AC:

40575

AN:

41500

American (AMR)

AF:

0.919

AC:

14043

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.924

AC:

3207

AN:

3472

East Asian (EAS)

AF:

0.997

AC:

5149

AN:

5162

South Asian (SAS)

AF:

0.942

AC:

4533

AN:

4810

European-Finnish (FIN)

AF:

0.867

AC:

9181

AN:

10590

Middle Eastern (MID)

AF:

0.922

AC:

271

AN:

294

European-Non Finnish (NFE)

AF:

0.879

AC:

59748

AN:

67992

Other (OTH)

AF:

0.912

AC:

1918

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

594

1189

1783

2378

2972

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

906

1812

2718

3624

4530

<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:

0.895

Hom.:

159763

Bravo

AF:

0.922

TwinsUK

AF:

0.872

AC:

3235

ALSPAC

AF:

0.879

AC:

3387

ESP6500AA

AF:

0.976

AC:

4300

ESP6500EA

AF:

0.883

AC:

7598

ExAC

AF:

0.909

AC:

110371

Asia WGS

AF:

0.962

AC:

3345

AN:

3478

EpiCase

AF:

0.885

EpiControl

AF:

0.879

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

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 99% of patients studied by a panel of primary immunodeficiencies. Number of patients: 94. Only high quality variants are reported. -

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 -

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

- -

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

0.090

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.53

CADD

Benign

0.30

(source)

DANN

Benign

0.48

DEOGEN2

Benign

0.00094

.;T;T;.;.;T;T

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.055

T;T;T;T;T;T;T

MetaRNN

Benign

8.2e-7

T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;N;.;N;.;.;.

PhyloP100

-0.19

PrimateAI

Benign

0.22

PROVEAN

Benign

1.4

N;N;N;N;N;N;N

REVEL

Benign

0.28

Sift

Benign

0.36

T;T;T;T;T;T;T

Sift4G

Benign

0.34

T;T;T;T;T;.;T

Polyphen

0.0030

B;B;B;.;.;.;.

Vest4

0.11

MutPred

0.45

Gain of disorder (P = 0.0043);Gain of disorder (P = 0.0043);Gain of disorder (P = 0.0043);Gain of disorder (P = 0.0043);.;Gain of disorder (P = 0.0043);.;

MPC

0.24

ClinPred

0.0023

GERP RS

-0.86

Varity_R

0.023

gMVP

0.18

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