Variant X-66022315-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_007268.3(VSIG4):c.1148C>T(p.Thr383Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00836 in 1,211,201 control chromosomes in the GnomAD database, including 26 homozygotes. There are 3,139 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0052 ( 0 hom., 147 hem., cov: 24)

Exomes 𝑓: 0.0087 ( 26 hom. 2992 hem. )

Consequence

VSIG4
NM_007268.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.920

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004070878).

BP6

Variant X-66022315-G-A is Benign according to our data. Variant chrX-66022315-G-A is described in ClinVar as [Benign]. Clinvar id is 779482.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-66022315-G-A is described in Lovd as [Likely_benign].

BS2

High Hemizygotes in GnomAd4 at 147 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VSIG4	NM_007268.3 link	c.1148C>T	p.Thr383Ile	missense_variant	8/8	ENST00000374737.9	NP_009199.1	Q9Y279-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VSIG4	ENST00000374737.9 link	c.1148C>T	p.Thr383Ile	missense_variant	8/8	1	NM_007268.3	ENSP00000363869.4		Q9Y279-1

Frequencies

GnomAD3 genomes

AF:

0.00516

AC:

584

AN:

113099

Hom.:

Cov.:

AF XY:

0.00417

AC XY:

147

AN XY:

35231

show subpopulations

Gnomad AFR

AF:

0.00141

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00250

Gnomad ASJ

AF:

0.00188

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00214

Gnomad FIN

AF:

0.00718

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00850

Gnomad OTH

AF:

0.00197

GnomAD3 exomes

AF:

0.00559

AC:

1021

AN:

182568

Hom.:

AF XY:

0.00578

AC XY:

389

AN XY:

67344

show subpopulations

Gnomad AFR exome

AF:

0.00122

Gnomad AMR exome

AF:

0.00175

Gnomad ASJ exome

AF:

0.00295

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00241

Gnomad FIN exome

AF:

0.00938

Gnomad NFE exome

AF:

0.00870

Gnomad OTH exome

AF:

0.00710

GnomAD4 exome

AF:

0.00869

AC:

9538

AN:

1098048

Hom.:

Cov.:

AF XY:

0.00823

AC XY:

2992

AN XY:

363468

show subpopulations

Gnomad4 AFR exome

AF:

0.00125

Gnomad4 AMR exome

AF:

0.00185

Gnomad4 ASJ exome

AF:

0.00258

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00233

Gnomad4 FIN exome

AF:

0.00943

Gnomad4 NFE exome

AF:

0.0101

Gnomad4 OTH exome

AF:

0.00738

GnomAD4 genome

AF:

0.00516

AC:

584

AN:

113153

Hom.:

Cov.:

AF XY:

0.00416

AC XY:

147

AN XY:

35295

show subpopulations

Gnomad4 AFR

AF:

0.00141

Gnomad4 AMR

AF:

0.00250

Gnomad4 ASJ

AF:

0.00188

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00215

Gnomad4 FIN

AF:

0.00718

Gnomad4 NFE

AF:

0.00851

Gnomad4 OTH

AF:

0.00194

Alfa

AF:

0.00769

Hom.:

320

Bravo

AF:

0.00444

TwinsUK

AF:

0.00917

AC:

ALSPAC

AF:

0.0128

AC:

ESP6500AA

AF:

0.00130

AC:

ESP6500EA

AF:

0.00817

AC:

ExAC

AF:

0.00588

AC:

714

EpiCase

AF:

0.00676

EpiControl

AF:

0.00889

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 08, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.60

CADD

Benign

9.8

DANN

Uncertain

0.98

DEOGEN2

Benign

0.067

T;.

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.66

T;T

MetaRNN

Benign

0.0041

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.97

L;.

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.3

N;N

REVEL

Benign

0.044

Sift

Uncertain

0.0040

D;D

Sift4G

Uncertain

0.015

D;D

Polyphen

0.23

B;P

Vest4

0.097

MVP

0.092

MPC

0.0059

ClinPred

0.013

GERP RS

2.7

Varity_R

0.079

gMVP

0.35

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