chrX-66033927-T-C

Variant names:

• chrX-66033927-T-C
• rs5964488
• NM_007268.3:c.56-97A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007268.3(VSIG4):​c.56-97A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 693,095 control chromosomes in the GnomAD database, including 18,154 homozygotes. There are 38,796 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 0.34 (8384 hom., 10692 hem., cov: 22)
  • Exomes 𝑓: 0.18 (9770 hom. 28104 hem.)
• Consequence: VSIG4 NM_007268.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0920
• Publications: 4 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.816 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007268.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VSIG4	NM_007268.3	MANE Select	c.56-97A>G		intron	N/A	NP_009199.1	Q9Y279-1
	VSIG4	NM_001257403.2		c.56-97A>G		intron	N/A	NP_001244332.1
	VSIG4	NM_001184830.2		c.56-97A>G		intron	N/A	NP_001171759.1	Q9Y279-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VSIG4	ENST00000374737.9	TSL:1 MANE Select	c.56-97A>G		intron	N/A	ENSP00000363869.4	Q9Y279-1
	VSIG4	ENST00000455586.6	TSL:1	c.56-97A>G		intron	N/A	ENSP00000411581.2	Q9Y279-2
	VSIG4	ENST00000968798.1		c.56-97A>G		intron	N/A	ENSP00000638857.1

Frequencies

GnomAD3 genomes AF: 0.341 AC: 37870 AN: 111151 Hom.: 8377 Cov.: 22

Gnomad AFR AF: 0.825

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.00167

Gnomad SAS AF: 0.0848

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.273

GnomAD4 exome AF: 0.177 AC: 102863 AN: 581889 Hom.: 9770 AF XY: 0.183 AC XY: 28104 AN XY: 153821

African (AFR) AF: 0.839 AC: 13087 AN: 15596

American (AMR) AF: 0.221 AC: 4681 AN: 21176

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 1494 AN: 11959

East Asian (EAS) AF: 0.00103 AC: 28 AN: 27073

South Asian (SAS) AF: 0.109 AC: 3738 AN: 34210

European-Finnish (FIN) AF: 0.180 AC: 6431 AN: 35640

Middle Eastern (MID) AF: 0.183 AC: 315 AN: 1726

European-Non Finnish (NFE) AF: 0.166 AC: 67591 AN: 406459

Other (OTH) AF: 0.196 AC: 5498 AN: 28050

GnomAD4 genome AF: 0.341 AC: 37940 AN: 111206 Hom.: 8384 Cov.: 22 AF XY: 0.319 AC XY: 10692 AN XY: 33470

African (AFR) AF: 0.825 AC: 25060 AN: 30382

American (AMR) AF: 0.224 AC: 2358 AN: 10524

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 335 AN: 2635

East Asian (EAS) AF: 0.00168 AC: 6 AN: 3574

South Asian (SAS) AF: 0.0865 AC: 232 AN: 2682

European-Finnish (FIN) AF: 0.164 AC: 981 AN: 5994

Middle Eastern (MID) AF: 0.186 AC: 40 AN: 215

European-Non Finnish (NFE) AF: 0.156 AC: 8268 AN: 53001

Other (OTH) AF: 0.273 AC: 416 AN: 1526

Alfa AF: 0.195 Hom.: 16019

Bravo AF: 0.368

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.5
DANN	Benign	0.70
PhyloP100		-0.092
PromoterAI		-0.021	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs5964488;

hg19: chrX-65253769;