Variant 2-36775067-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_053276.4(VIT):c.802G>C(p.Gly268Arg) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00156 in 1,613,566 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0016 ( 7 hom. )

Consequence

VIT
NM_053276.4 missense, splice_region

Scores

Splicing: ADA: 1.000

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.41

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 -6 ACMG points.

BP6

Variant 2-36775067-G-C is Benign according to our data. Variant chr2-36775067-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 710543.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VIT	NM_053276.4 link	c.802G>C	p.Gly268Arg	missense_variant, splice_region_variant	9/16	ENST00000379242.8	NP_444506.2	Q6UXI7-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VIT	ENST00000379242.8 link	c.802G>C	p.Gly268Arg	missense_variant, splice_region_variant	9/16	2	NM_053276.4	ENSP00000368544.3		Q6UXI7-4

Frequencies

GnomAD3 genomes

AF:

0.00115

AC:

175

AN:

152064

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000459

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000655

Gnomad ASJ

AF:

0.00634

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00179

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.000840

AC:

211

AN:

251128

Hom.:

AF XY:

0.000832

AC XY:

113

AN XY:

135736

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.000463

Gnomad ASJ exome

AF:

0.00557

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00110

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.00160

AC:

2343

AN:

1461502

Hom.:

Cov.:

AF XY:

0.00150

AC XY:

1093

AN XY:

727038

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.000403

Gnomad4 ASJ exome

AF:

0.00582

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.00182

Gnomad4 OTH exome

AF:

0.00224

GnomAD4 genome

AF:

0.00115

AC:

175

AN:

152064

Hom.:

Cov.:

AF XY:

0.000848

AC XY:

AN XY:

74252

show subpopulations

Gnomad4 AFR

AF:

0.000459

Gnomad4 AMR

AF:

0.000655

Gnomad4 ASJ

AF:

0.00634

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00179

Gnomad4 OTH

AF:

0.000955

Alfa

AF:

0.00177

Hom.:

Bravo

AF:

0.00114

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00198

AC:

ExAC

AF:

0.000733

AC:

EpiCase

AF:

0.00207

EpiControl

AF:

0.00136

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 15, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Uncertain

-0.080

CADD

Benign

DANN

Uncertain

1.0

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.33

MetaRNN

Benign

0.019

MetaSVM

Benign

-0.64

PROVEAN

Benign

-2.1

REVEL

Benign

0.11

Sift

Uncertain

0.011

Sift4G

Uncertain

0.018

Vest4

0.52

MVP

0.44

ClinPred

0.031

GERP RS

4.8

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.98

SpliceAI score (max)

0.26

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.26

Position offset: 0

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