Variant chr2-36773813-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_053276.4(VIT):c.702C>G(p.Tyr234Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0103 in 1,604,824 control chromosomes in the GnomAD database, including 100 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.0081 ( 15 hom., cov: 32)

Exomes 𝑓: 0.011 ( 85 hom. )

Consequence

VIT
NM_053276.4 stop_gained

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.202

Variant links:

Genes affected

VIT (HGNC:12697): (vitrin) This gene encodes an extracellular matrix (ECM) protein. The protein may be associated with cell adhesion and migration. High levels of expression of the protein in specific parts of the brain suggest its likely role in neural development. [provided by RefSeq, Jun 2016]

VIT links:

LOC124905990 (HGNC:):

LOC124905990 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High Homozygotes in GnomAd4 at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VIT	NM_053276.4 linkuse as main transcript	c.702C>G	p.Tyr234Ter	stop_gained	8/16	ENST00000379242.8	NP_444506.2
LOC124905990	XR_007086283.1 linkuse as main transcript	n.231-9078G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VIT	ENST00000379242.8 linkuse as main transcript	c.702C>G	p.Tyr234Ter	stop_gained	8/16	2	NM_053276.4	ENSP00000368544	A2	Q6UXI7-4

Frequencies

GnomAD3 genomes

AF:

0.00807

AC:

1228

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00667

Gnomad ASJ

AF:

0.00720

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.0126

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0122

Gnomad OTH

AF:

0.00861

GnomAD3 exomes

AF:

0.00799

AC:

1997

AN:

249982

Hom.:

AF XY:

0.00799

AC XY:

1080

AN XY:

135120

show subpopulations

Gnomad AFR exome

AF:

0.00223

Gnomad AMR exome

AF:

0.00399

Gnomad ASJ exome

AF:

0.00667

Gnomad EAS exome

AF:

0.0000551

Gnomad SAS exome

AF:

0.000756

Gnomad FIN exome

AF:

0.0131

Gnomad NFE exome

AF:

0.0125

Gnomad OTH exome

AF:

0.00673

GnomAD4 exome

AF:

0.0105

AC:

15277

AN:

1452502

Hom.:

Cov.:

AF XY:

0.0102

AC XY:

7394

AN XY:

722498

show subpopulations

Gnomad4 AFR exome

AF:

0.00216

Gnomad4 AMR exome

AF:

0.00413

Gnomad4 ASJ exome

AF:

0.00657

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.000805

Gnomad4 FIN exome

AF:

0.0117

Gnomad4 NFE exome

AF:

0.0123

Gnomad4 OTH exome

AF:

0.00870

GnomAD4 genome

AF:

0.00806

AC:

1228

AN:

152322

Hom.:

Cov.:

AF XY:

0.00785

AC XY:

585

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.00265

Gnomad4 AMR

AF:

0.00666

Gnomad4 ASJ

AF:

0.00720

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.0126

Gnomad4 NFE

AF:

0.0122

Gnomad4 OTH

AF:

0.00852

Alfa

AF:

0.00976

Hom.:

Bravo

AF:

0.00779

TwinsUK

AF:

0.0108

AC:

ALSPAC

AF:

0.0138

AC:

ESP6500AA

AF:

0.00227

AC:

ESP6500EA

AF:

0.0122

AC:

105

ExAC

AF:

0.00819

AC:

995

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 01, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.058

BayesDel_noAF

Pathogenic

0.16

CADD

Pathogenic

DANN

Uncertain

0.99

Eigen

Benign

-0.12

Eigen_PC

Benign

-0.43

FATHMM_MKL

Benign

0.13

MutationTaster

Benign

1.0

A;A;A;A;N;N

Vest4

0.77

ClinPred

0.095

GERP RS

0.71

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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