10-71773420-A-G

Position:

chr10-71773420-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_022153.2(VSIR):c.20T>C(p.Leu7Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.415 in 1,603,072 control chromosomes in the GnomAD database, including 141,814 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.37 ( 10752 hom., cov: 34)

Exomes 𝑓: 0.42 ( 131062 hom. )

Consequence

VSIR
NM_022153.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.61

Variant links:

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]

VSIR links:

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]

CDH23 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.3959408E-4).

BP6

Variant 10-71773420-A-G is Benign according to our data. Variant chr10-71773420-A-G is described in ClinVar as [Benign]. Clinvar id is 802587.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.464 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VSIR	NM_022153.2 link	c.20T>C	p.Leu7Pro	missense_variant	1/7	ENST00000394957.8	NP_071436.1	Q9H7M9
CDH23	NM_022124.6 link	c.4846-4260A>G		intron_variant		ENST00000224721.12	NP_071407.4	Q9H251-1Q6P152

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VSIR	ENST00000394957.8 link	c.20T>C	p.Leu7Pro	missense_variant	1/7	1	NM_022153.2	ENSP00000378409.3		Q9H7M9
CDH23	ENST00000224721.12 link	c.4846-4260A>G		intron_variant		5	NM_022124.6	ENSP00000224721.9		Q9H251-1

Frequencies

GnomAD3 genomes

AF:

0.367

AC:

55770

AN:

152106

Hom.:

10751

Cov.:

show subpopulations

Gnomad AFR

AF:

0.270

Gnomad AMI

AF:

0.399

Gnomad AMR

AF:

0.332

Gnomad ASJ

AF:

0.468

Gnomad EAS

AF:

0.197

Gnomad SAS

AF:

0.481

Gnomad FIN

AF:

0.361

Gnomad MID

AF:

0.478

Gnomad NFE

AF:

0.432

Gnomad OTH

AF:

0.381

GnomAD3 exomes

AF:

0.387

AC:

87113

AN:

224918

Hom.:

17652

AF XY:

0.403

AC XY:

49668

AN XY:

123270

show subpopulations

Gnomad AFR exome

AF:

0.269

Gnomad AMR exome

AF:

0.276

Gnomad ASJ exome

AF:

0.468

Gnomad EAS exome

AF:

0.200

Gnomad SAS exome

AF:

0.500

Gnomad FIN exome

AF:

0.358

Gnomad NFE exome

AF:

0.436

Gnomad OTH exome

AF:

0.402

GnomAD4 exome

AF:

0.420

AC:

609488

AN:

1450848

Hom.:

131062

Cov.:

AF XY:

0.424

AC XY:

305306

AN XY:

720838

show subpopulations

Gnomad4 AFR exome

AF:

0.260

Gnomad4 AMR exome

AF:

0.276

Gnomad4 ASJ exome

AF:

0.462

Gnomad4 EAS exome

AF:

0.185

Gnomad4 SAS exome

AF:

0.496

Gnomad4 FIN exome

AF:

0.364

Gnomad4 NFE exome

AF:

0.435

Gnomad4 OTH exome

AF:

0.406

GnomAD4 genome

AF:

0.366

AC:

55783

AN:

152224

Hom.:

10752

Cov.:

AF XY:

0.366

AC XY:

27224

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.270

Gnomad4 AMR

AF:

0.331

Gnomad4 ASJ

AF:

0.468

Gnomad4 EAS

AF:

0.198

Gnomad4 SAS

AF:

0.480

Gnomad4 FIN

AF:

0.361

Gnomad4 NFE

AF:

0.432

Gnomad4 OTH

AF:

0.382

Alfa

AF:

0.409

Hom.:

11044

Bravo

AF:

0.355

TwinsUK

AF:

0.434

AC:

1609

ALSPAC

AF:

0.443

AC:

1708

ESP6500AA

AF:

0.273

AC:

1188

ESP6500EA

AF:

0.426

AC:

3634

ExAC

AF:

0.374

AC:

44769

Asia WGS

AF:

0.317

AC:

1106

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Retinitis pigmentosa-deafness syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Mendelics

May 28, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.032

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.70

CADD

Benign

DANN

Benign

0.74

DEOGEN2

Benign

0.00034

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.00040

LIST_S2

Benign

0.20

MetaRNN

Benign

0.00014

MetaSVM

Benign

-0.90

PROVEAN

Benign

2.3

REVEL

Benign

0.051

Sift

Benign

1.0

Sift4G

Benign

0.098

Polyphen

0.0

Vest4

0.062

MPC

0.41

ClinPred

0.00059

GERP RS

2.0

Varity_R

0.090

gMVP

0.83

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