10-71751847-A-G

Position:

• chr10-71751847-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_022153.2(VSIR):​c.719T>C​(p.Ile240Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000809 in 1,554,652 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00055 (2 hom., cov: 31)
  • Exomes 𝑓: 0.00084 (11 hom.)
• Consequence: VSIR NM_022153.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.68

Genes affected

VSIR (HGNC:30085): (V-set immunoregulatory receptor) Enables endopeptidase activator activity; enzyme binding activity; and identical protein binding activity. Involved in several processes, including negative regulation of cytokine production; positive regulation of macromolecule metabolic process; and regulation of T cell activation. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

CDH23 (HGNC:13733): (cadherin related 23) This gene is a member of the cadherin superfamily, whose genes encode calcium dependent cell-cell adhesion glycoproteins. The encoded protein is thought to be involved in stereocilia organization and hair bundle formation. The gene is located in a region containing the human deafness loci DFNB12 and USH1D. Usher syndrome 1D and nonsyndromic autosomal recessive deafness DFNB12 are caused by allelic mutations of this cadherin-like gene. Upregulation of this gene may also be associated with breast cancer. Alternative splice variants encoding different isoforms have been described. [provided by RefSeq, May 2013]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.010266542).
• BP6: Variant 10-71751847-A-G is Benign according to our data. Variant chr10-71751847-A-G is described in ClinVar as [Benign]. Clinvar id is 3250521.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VSIR	NM_022153.2	c.719T>C	p.Ile240Thr	missense_variant	6/7	ENST00000394957.8	NP_071436.1
CDH23	NM_022124.6	c.4845+9926A>G		intron_variant		ENST00000224721.12	NP_071407.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VSIR	ENST00000394957.8	c.719T>C	p.Ile240Thr	missense_variant	6/7	1	NM_022153.2	ENSP00000378409	P1
CDH23	ENST00000224721.12	c.4845+9926A>G		intron_variant		5	NM_022124.6	ENSP00000224721	P1
VSIR	ENST00000470317.2	n.204T>C		non_coding_transcript_exon_variant	4/5	5

Frequencies

GnomAD3 genomes AF: 0.000565 AC: 86 AN: 152132 Hom.: 2 Cov.: 31

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.00230

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0112

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.000955

GnomAD3 exomes AF: 0.00146 AC: 297 AN: 204004 Hom.: 3 AF XY: 0.00177 AC XY: 193 AN XY: 109306

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000538

Gnomad ASJ exome AF: 0.00259

Gnomad EAS exome AF: 0.0000605

Gnomad SAS exome AF: 0.0104

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000295

Gnomad OTH exome AF: 0.00295

GnomAD4 exome AF: 0.000836 AC: 1173 AN: 1402402 Hom.: 11 Cov.: 31 AF XY: 0.00104 AC XY: 722 AN XY: 692358

Gnomad4 AFR exome AF: 0.0000318

Gnomad4 AMR exome AF: 0.000639

Gnomad4 ASJ exome AF: 0.00337

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00969

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000216

Gnomad4 OTH exome AF: 0.00108

GnomAD4 genome AF: 0.000552 AC: 84 AN: 152250 Hom.: 2 Cov.: 31 AF XY: 0.000725 AC XY: 54 AN XY: 74436

Gnomad4 AFR AF: 0.0000722

Gnomad4 AMR AF: 0.000392

Gnomad4 ASJ AF: 0.00230

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0108

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000176

Gnomad4 OTH AF: 0.000945

Alfa AF: 0.000549 Hom.: 0

Bravo AF: 0.000374

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00162 AC: 196

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jun 01, 2024

VSIR: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.093	T
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.85	T
MetaRNN	Benign	0.010	T
MetaSVM	Benign	-0.86	T
MutationTaster	Benign	1.0	D;D
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.16
Sift	Benign	0.070	T
Sift4G	Benign	0.22	T
Polyphen		0.81	P
Vest4		0.68
MVP		0.40
MPC		0.53
ClinPred		0.031	T
GERP RS		5.8
Varity_R		0.099
gMVP		0.12

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

Other links and lift over

dbSNP: rs151170391; hg19: chr10-73511604;