Variant X-66028042-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The ENST00000374737.9(VSIG4):c.757+8T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00155 in 1,207,365 control chromosomes in the GnomAD database, including 2 homozygotes. There are 639 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00093 ( 0 hom., 27 hem., cov: 23)

Exomes 𝑓: 0.0016 ( 2 hom. 612 hem. )

Consequence

VSIG4
ENST00000374737.9 splice_region, intron

Scores

Splicing: ADA: 0.00003455

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.711

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant X-66028042-A-G is Benign according to our data. Variant chrX-66028042-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3052435.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Hemizygotes in GnomAd4 at 27 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VSIG4	NM_007268.3 linkuse as main transcript	c.757+8T>C		splice_region_variant, intron_variant		ENST00000374737.9	NP_009199.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VSIG4	ENST00000374737.9 linkuse as main transcript	c.757+8T>C		splice_region_variant, intron_variant		1	NM_007268.3	ENSP00000363869	P2	Q9Y279-1

Frequencies

GnomAD3 genomes

AF:

0.000930

AC:

104

AN:

111883

Hom.:

Cov.:

AF XY:

0.000793

AC XY:

AN XY:

34051

show subpopulations

Gnomad AFR

AF:

0.000163

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000285

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000744

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00177

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000848

AC:

155

AN:

182876

Hom.:

AF XY:

0.00107

AC XY:

AN XY:

67532

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000256

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000145

Gnomad SAS exome

AF:

0.00199

Gnomad FIN exome

AF:

0.000125

Gnomad NFE exome

AF:

0.00125

Gnomad OTH exome

AF:

0.000888

GnomAD4 exome

AF:

0.00161

AC:

1764

AN:

1095430

Hom.:

Cov.:

AF XY:

0.00169

AC XY:

612

AN XY:

361230

show subpopulations

Gnomad4 AFR exome

AF:

0.000228

Gnomad4 AMR exome

AF:

0.000256

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000133

Gnomad4 SAS exome

AF:

0.00213

Gnomad4 FIN exome

AF:

0.0000494

Gnomad4 NFE exome

AF:

0.00187

Gnomad4 OTH exome

AF:

0.00117

GnomAD4 genome

AF:

0.000929

AC:

104

AN:

111935

Hom.:

Cov.:

AF XY:

0.000791

AC XY:

AN XY:

34113

show subpopulations

Gnomad4 AFR

AF:

0.000162

Gnomad4 AMR

AF:

0.000284

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000747

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00177

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00167

Hom.:

Bravo

AF:

0.000903

EpiCase

AF:

0.00137

EpiControl

AF:

0.000416

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

Oct 07, 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

-0.67

CADD

Benign

4.1

DANN

Benign

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000035

dbscSNV1_RF

Benign

0.0

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