Genetic Variant NM_007268.3:c.56-97A>T (chrX-66033927-T-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_007268.3(VSIG4):c.56-97A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000173 in 693,740 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000090 ( 0 hom., 0 hem., cov: 22)

Exomes 𝑓: 0.000019 ( 0 hom. 4 hem. )

Consequence

VSIG4
NM_007268.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0920

Publications

4 publications found

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 was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BS2

High Hemizygotes in GnomAdExome4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VSIG4	NM_007268.3 link	c.56-97A>T		intron_variant	Intron 1 of 7	ENST00000374737.9	NP_009199.1	Q9Y279-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
VSIG4	ENST00000374737.9 link	c.56-97A>T	intron_variant	Intron 1 of 7	1	NM_007268.3	ENSP00000363869.4	Q9Y279-1
VSIG4	ENST00000455586.6 link	c.56-97A>T	intron_variant	Intron 1 of 6	1		ENSP00000411581.2	Q9Y279-2
VSIG4	ENST00000412866.2 link	c.56-97A>T	intron_variant	Intron 1 of 6	2		ENSP00000394143.2	Q9Y279-3
VSIG4	ENST00000651578.1 link	n.56-97A>T	intron_variant	Intron 1 of 8			ENSP00000498502.1	A0A494C0F5

Frequencies

GnomAD3 genomes

AF:

0.00000899

AC:

AN:

111192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000189

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000189

AC:

AN:

582548

Hom.:

AF XY:

0.0000260

AC XY:

AN XY:

153920

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

15606

American (AMR)

AF:

0.00

AC:

AN:

21216

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

11963

East Asian (EAS)

AF:

0.00

AC:

AN:

27073

South Asian (SAS)

AF:

0.00

AC:

AN:

34223

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35662

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1726

European-Non Finnish (NFE)

AF:

0.0000270

AC:

AN:

407003

Other (OTH)

AF:

0.00

AC:

AN:

28076

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.00000899

AC:

AN:

111192

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33422

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30327

American (AMR)

AF:

0.00

AC:

AN:

10520

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2635

East Asian (EAS)

AF:

0.00

AC:

AN:

3585

South Asian (SAS)

AF:

0.00

AC:

AN:

2689

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5998

Middle Eastern (MID)

AF:

0.00

AC:

AN:

236

European-Non Finnish (NFE)

AF:

0.0000189

AC:

AN:

53021

Other (OTH)

AF:

0.00

AC:

AN:

1508

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

16019

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.3

(source)

DANN

Benign

0.79

PhyloP100

-0.092

PromoterAI

-0.00080

Neutral

(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

Computational scores

Splicing

Publications

Other links and lift over