2-230212968-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_080424.4(SP110):c.376G>A(p.Gly126Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0152 in 1,613,966 control chromosomes in the GnomAD database, including 315 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 0.014 ( 44 hom., cov: 31)

Exomes 𝑓: 0.015 ( 271 hom. )

Consequence

SP110
NM_080424.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.240

Publications

8 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=0.0027492046).

BP6

Variant 2-230212968-C-T is Benign according to our data. Variant chr2-230212968-C-T is described in ClinVar as Benign. ClinVar VariationId is 334918.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0144 (2188/152142) while in subpopulation NFE AF = 0.0171 (1165/67990). AF 95% confidence interval is 0.0163. There are 44 homozygotes in GnomAd4. There are 1172 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 44 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SP110	NM_080424.4 link	c.376G>A	p.Gly126Ser	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.376G>A	p.Gly126Ser	missense_variant	Exon 4 of 19	2	NM_080424.4	ENSP00000258381.6		Q9HB58-6

Frequencies

GnomAD3 genomes

AF:

0.0144

AC:

2188

AN:

152024

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00191

Gnomad AMI

AF:

0.0132

Gnomad AMR

AF:

0.0115

Gnomad ASJ

AF:

0.0196

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00643

Gnomad FIN

AF:

0.0589

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0171

Gnomad OTH

AF:

0.0135

GnomAD2 exomes

AF:

0.0163

AC:

4084

AN:

250082

AF XY:

0.0165

show subpopulations

Gnomad AFR exome

AF:

0.00215

Gnomad AMR exome

AF:

0.0104

Gnomad ASJ exome

AF:

0.0195

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.0579

Gnomad NFE exome

AF:

0.0172

Gnomad OTH exome

AF:

0.0209

GnomAD4 exome

AF:

0.0153

AC:

22418

AN:

1461824

Hom.:

271

Cov.:

AF XY:

0.0152

AC XY:

11046

AN XY:

727218

show subpopulations

African (AFR)

AF:

0.00170

AC:

AN:

33480

American (AMR)

AF:

0.0103

AC:

460

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0210

AC:

549

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39690

South Asian (SAS)

AF:

0.00580

AC:

500

AN:

86258

European-Finnish (FIN)

AF:

0.0548

AC:

2928

AN:

53416

Middle Eastern (MID)

AF:

0.00815

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0153

AC:

17001

AN:

1111960

Other (OTH)

AF:

0.0145

AC:

876

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

1233

2467

3700

4934

6167

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

608

1216

1824

2432

3040

<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:

0.0144

AC:

2188

AN:

152142

Hom.:

Cov.:

AF XY:

0.0158

AC XY:

1172

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.00190

AC:

AN:

41528

American (AMR)

AF:

0.0114

AC:

175

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0196

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5162

South Asian (SAS)

AF:

0.00664

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.0589

AC:

623

AN:

10582

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0171

AC:

1165

AN:

67990

Other (OTH)

AF:

0.0128

AC:

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

107

214

322

429

536

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

<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:

0.0150

Hom.:

Bravo

AF:

0.00975

TwinsUK

AF:

0.0200

AC:

ALSPAC

AF:

0.0179

AC:

ESP6500AA

AF:

0.00227

AC:

ESP6500EA

AF:

0.0170

AC:

146

ExAC

AF:

0.0154

AC:

1874

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.0175

EpiControl

AF:

0.0210

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hepatic veno-occlusive disease-immunodeficiency syndrome

Benign:2

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

0.084

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.66

CADD

Benign

4.9

(source)

DANN

Benign

0.65

DEOGEN2

Benign

0.0012

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

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.024

LIST_S2

Benign

0.66

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

MetaRNN

Benign

0.0027

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

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.34

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

PhyloP100

0.24

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.57

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

REVEL

Benign

0.044

Sift

Benign

0.097

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

Sift4G

Benign

0.37

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

Polyphen

0.037

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

Vest4

0.099

MPC

0.56

ClinPred

0.0071

GERP RS

0.90

Varity_R

0.024

gMVP

0.22

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