chr12-53192752-C-T

Position:

chr12-53192752-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000889.3(ITGB7):c.1885G>A(p.Gly629Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0049 in 1,614,220 control chromosomes in the GnomAD database, including 91 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0057 ( 11 hom., cov: 32)

Exomes 𝑓: 0.0048 ( 80 hom. )

Consequence

ITGB7
NM_000889.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.44

Variant links:

Genes affected

ITGB7 (HGNC:6162): (integrin subunit beta 7) This gene encodes a protein that is a member of the integrin superfamily. Members of this family are adhesion receptors that function in signaling from the extracellular matrix to the cell. Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain. The encoded protein forms dimers with an alpha4 chain or an alphaE chain and plays a role in leukocyte adhesion. Dimerization with alpha4 forms a homing receptor for migration of lymphocytes to the intestinal mucosa and Peyer's patches. Dimerization with alphaE permits binding to the ligand epithelial cadherin, a calcium-dependent adhesion molecule. Alternate splicing results in multiple transcript variants. Additional alternatively spliced transcript variants of this gene have been described, but their full-length nature is not known. [provided by RefSeq, Sep 2013]

ITGB7 links:

ZNF740 (HGNC:27465): (zinc finger protein 740) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. Predicted to be part of chromatin. [provided by Alliance of Genome Resources, Apr 2022]

ZNF740 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=0.011388004).

BP6

Variant 12-53192752-C-T is Benign according to our data. Variant chr12-53192752-C-T is described in ClinVar as [Benign]. Clinvar id is 771458.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00573 (873/152346) while in subpopulation SAS AF= 0.0221 (107/4832). AF 95% confidence interval is 0.0187. There are 11 homozygotes in gnomad4. There are 529 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITGB7	NM_000889.3 linkuse as main transcript	c.1885G>A	p.Gly629Ser	missense_variant	13/16	ENST00000267082.10
ZNF740	NM_001004304.4 linkuse as main transcript	c.*5162C>T		3_prime_UTR_variant	7/7	ENST00000416904.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGB7	ENST00000267082.10 linkuse as main transcript	c.1885G>A	p.Gly629Ser	missense_variant	13/16	1	NM_000889.3	P1	P26010-1
ZNF740	ENST00000416904.5 linkuse as main transcript	c.*5162C>T		3_prime_UTR_variant	7/7	1	NM_001004304.4	P1

Frequencies

GnomAD3 genomes

AF:

0.00573

AC:

872

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00152

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0172

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.0221

Gnomad FIN

AF:

0.0193

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00314

Gnomad OTH

AF:

0.00813

GnomAD3 exomes

AF:

0.00935

AC:

2349

AN:

251156

Hom.:

AF XY:

0.00959

AC XY:

1302

AN XY:

135760

show subpopulations

Gnomad AFR exome

AF:

0.00105

Gnomad AMR exome

AF:

0.0243

Gnomad ASJ exome

AF:

0.000298

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0251

Gnomad FIN exome

AF:

0.0184

Gnomad NFE exome

AF:

0.00248

Gnomad OTH exome

AF:

0.00700

GnomAD4 exome

AF:

0.00481

AC:

7037

AN:

1461874

Hom.:

Cov.:

AF XY:

0.00544

AC XY:

3957

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.000747

Gnomad4 AMR exome

AF:

0.0228

Gnomad4 ASJ exome

AF:

0.000344

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0246

Gnomad4 FIN exome

AF:

0.0175

Gnomad4 NFE exome

AF:

0.00236

Gnomad4 OTH exome

AF:

0.00447

GnomAD4 genome

AF:

0.00573

AC:

873

AN:

152346

Hom.:

Cov.:

AF XY:

0.00710

AC XY:

529

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.00151

Gnomad4 AMR

AF:

0.0172

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.0221

Gnomad4 FIN

AF:

0.0193

Gnomad4 NFE

AF:

0.00315

Gnomad4 OTH

AF:

0.00804

Alfa

AF:

0.00216

Hom.:

Bravo

AF:

0.00471

TwinsUK

AF:

0.00297

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00291

AC:

ExAC

AF:

0.00818

AC:

993

Asia WGS

AF:

0.0110

AC:

AN:

3478

EpiCase

AF:

0.00262

EpiControl

AF:

0.00172

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	Mar 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Uncertain

0.060

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.73

D;D

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.51

.;T

MetaRNN

Benign

0.011

T;T

MetaSVM

Uncertain

0.32

MutationAssessor

Pathogenic

3.0

M;M

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.51

PROVEAN

Uncertain

-3.1

D;D

REVEL

Pathogenic

0.67

Sift

Benign

0.13

T;T

Sift4G

Benign

0.17

T;T

Polyphen

1.0

D;D

Vest4

0.37

MVP

0.94

MPC

0.98

ClinPred

0.027

GERP RS

5.1

Varity_R

0.18

gMVP

0.60

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