Variant X-66022136-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2

The NM_001257403.2(VSIG4):c.993C>T(p.Ala331Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000368 in 1,192,079 control chromosomes in the GnomAD database, including 1 homozygotes. There are 131 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., 9 hem., cov: 24)

Exomes 𝑓: 0.00038 ( 1 hom. 122 hem. )

Consequence

VSIG4
NM_001257403.2 synonymous

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.882

Variant links:

Genes affected

VSIG4 (HGNC:17032): (V-set and immunoglobulin domain containing 4) This gene encodes a v-set and immunoglobulin-domain containing protein that is structurally related to the B7 family of immune regulatory proteins. The encoded protein may be a negative regulator of T-cell responses. This protein is also a receptor for the complement component 3 fragments C3b and iC3b. Alternate splicing results in multiple transcript variants. [provided by RefSeq, May 2010]

VSIG4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant X-66022136-G-A is Benign according to our data. Variant chrX-66022136-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3035869.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.882 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 9 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VSIG4	NM_007268.3 link	c.*127C>T		3_prime_UTR_variant	8/8	ENST00000374737.9	NP_009199.1	Q9Y279-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VSIG4	ENST00000374737 link	c.*127C>T		3_prime_UTR_variant	8/8	1	NM_007268.3	ENSP00000363869.4		Q9Y279-1

Frequencies

GnomAD3 genomes

AF:

0.000240

AC:

AN:

112322

Hom.:

Cov.:

AF XY:

0.000261

AC XY:

AN XY:

34488

show subpopulations

Gnomad AFR

AF:

0.0000970

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000283

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000364

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000376

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000172

AC:

AN:

145754

Hom.:

AF XY:

0.000111

AC XY:

AN XY:

45054

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000839

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000616

Gnomad FIN exome

AF:

0.0000706

Gnomad NFE exome

AF:

0.000329

Gnomad OTH exome

AF:

0.000261

GnomAD4 exome

AF:

0.000382

AC:

412

AN:

1079702

Hom.:

Cov.:

AF XY:

0.000346

AC XY:

122

AN XY:

352382

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000616

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000171

Gnomad4 SAS exome

AF:

0.000232

Gnomad4 FIN exome

AF:

0.0000510

Gnomad4 NFE exome

AF:

0.000460

Gnomad4 OTH exome

AF:

0.000176

GnomAD4 genome

AF:

0.000240

AC:

AN:

112377

Hom.:

Cov.:

AF XY:

0.000260

AC XY:

AN XY:

34553

show subpopulations

Gnomad4 AFR

AF:

0.0000968

Gnomad4 AMR

AF:

0.000283

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000365

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000376

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.000174

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

VSIG4-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 01, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.34

DANN

Benign

0.52

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over