Variant X-66022347-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_007268.3(VSIG4):c.1116G>C(p.Gln372His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000438 in 1,211,124 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 17 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., 6 hem., cov: 24)

Exomes 𝑓: 0.000032 ( 0 hom. 11 hem. )

Consequence

VSIG4
NM_007268.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.449

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.053165674).

BS2

High Hemizygotes in GnomAd4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VSIG4	NM_007268.3 link	c.1116G>C	p.Gln372His	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.1116G>C	p.Gln372His	missense_variant	8/8	1	NM_007268.3	ENSP00000363869.4		Q9Y279-1

Frequencies

GnomAD3 genomes

AF:

0.000159

AC:

AN:

113047

Hom.:

Cov.:

AF XY:

0.000171

AC XY:

AN XY:

35187

show subpopulations

Gnomad AFR

AF:

0.000514

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000925

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000652

GnomAD3 exomes

AF:

0.0000712

AC:

AN:

182471

Hom.:

AF XY:

0.0000743

AC XY:

AN XY:

67305

show subpopulations

Gnomad AFR exome

AF:

0.000762

Gnomad AMR exome

AF:

0.0000365

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000246

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000319

AC:

AN:

1098023

Hom.:

Cov.:

AF XY:

0.0000303

AC XY:

AN XY:

363469

show subpopulations

Gnomad4 AFR exome

AF:

0.000909

Gnomad4 AMR exome

AF:

0.0000852

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000475

Gnomad4 OTH exome

AF:

0.0000868

GnomAD4 genome

AF:

0.000159

AC:

AN:

113101

Hom.:

Cov.:

AF XY:

0.000170

AC XY:

AN XY:

35251

show subpopulations

Gnomad4 AFR

AF:

0.000513

Gnomad4 AMR

AF:

0.0000924

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000644

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.000155

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000412

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 11, 2024

The c.1116G>C (p.Q372H) alteration is located in exon 8 (coding exon 8) of the VSIG4 gene. This alteration results from a G to C substitution at nucleotide position 1116, causing the glutamine (Q) at amino acid position 372 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.68

CADD

Benign

8.7

DANN

Uncertain

0.99

DEOGEN2

Benign

0.049

T;.

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.71

T;T

M_CAP

Benign

0.0025

MetaRNN

Benign

0.053

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.97

L;.

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.016

Sift

Benign

0.073

T;D

Sift4G

Benign

0.13

T;D

Polyphen

0.088

B;B

Vest4

0.17

MutPred

0.27

Gain of sheet (P = 0.1208);.;

MVP

0.19

MPC

0.0048

ClinPred

0.017

GERP RS

2.7

Varity_R

0.078

gMVP

0.42

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