chr12-53192471-G-A

Position:

chr12-53192471-G-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_000889.3(ITGB7):c.2014C>T(p.His672Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0116 in 1,614,176 control chromosomes in the GnomAD database, including 124 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.0087 ( 5 hom., cov: 32)

Exomes 𝑓: 0.012 ( 119 hom. )

Consequence

ITGB7
NM_000889.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.393

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0045182407).

BP6

Variant 12-53192471-G-A is Benign according to our data. Variant chr12-53192471-G-A is described in ClinVar as [Benign]. Clinvar id is 791425.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGB7	NM_000889.3 link	c.2014C>T	p.His672Tyr	missense_variant	14/16	ENST00000267082.10	NP_000880.1	P26010-1
ZNF740	NM_001004304.4 link	c.*4881G>A		3_prime_UTR_variant	7/7	ENST00000416904.5	NP_001004304.1	Q8NDX6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGB7	ENST00000267082.10 link	c.2014C>T	p.His672Tyr	missense_variant	14/16	1	NM_000889.3	ENSP00000267082.4		P26010-1
ZNF740	ENST00000416904.5 link	c.*4881G>A		3_prime_UTR_variant	7/7	1	NM_001004304.4	ENSP00000409463.2		Q8NDX6

Frequencies

GnomAD3 genomes

AF:

0.00870

AC:

1324

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00224

Gnomad AMI

AF:

0.00768

Gnomad AMR

AF:

0.00831

Gnomad ASJ

AF:

0.00432

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00393

Gnomad FIN

AF:

0.00745

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0143

Gnomad OTH

AF:

0.00525

GnomAD3 exomes

AF:

0.00841

AC:

2110

AN:

250872

Hom.:

AF XY:

0.00883

AC XY:

1198

AN XY:

135644

show subpopulations

Gnomad AFR exome

AF:

0.00203

Gnomad AMR exome

AF:

0.00460

Gnomad ASJ exome

AF:

0.00706

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00323

Gnomad FIN exome

AF:

0.00800

Gnomad NFE exome

AF:

0.0134

Gnomad OTH exome

AF:

0.00848

GnomAD4 exome

AF:

0.0119

AC:

17341

AN:

1461872

Hom.:

119

Cov.:

AF XY:

0.0116

AC XY:

8452

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.00164

Gnomad4 AMR exome

AF:

0.00510

Gnomad4 ASJ exome

AF:

0.00735

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00288

Gnomad4 FIN exome

AF:

0.00904

Gnomad4 NFE exome

AF:

0.0139

Gnomad4 OTH exome

AF:

0.0104

GnomAD4 genome

AF:

0.00871

AC:

1326

AN:

152304

Hom.:

Cov.:

AF XY:

0.00815

AC XY:

607

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.00224

Gnomad4 AMR

AF:

0.00830

Gnomad4 ASJ

AF:

0.00432

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00434

Gnomad4 FIN

AF:

0.00745

Gnomad4 NFE

AF:

0.0143

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.0127

Hom.:

Bravo

AF:

0.00832

TwinsUK

AF:

0.0156

AC:

ALSPAC

AF:

0.0135

AC:

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.0134

AC:

115

ExAC

AF:

0.00854

AC:

1037

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.0132

EpiControl

AF:

0.0129

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	May 21, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.27

T;T;.

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.32

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.59

.;T;T

MetaRNN

Benign

0.0045

T;T;T

MetaSVM

Uncertain

-0.059

MutationAssessor

Benign

1.2

L;L;.

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.3

N;N;.

REVEL

Benign

0.11

Sift

Benign

0.41

T;T;.

Sift4G

Benign

0.81

T;T;T

Polyphen

0.12

B;B;.

Vest4

0.12

MVP

0.82

MPC

0.44

ClinPred

0.0031

GERP RS

2.4

Varity_R

0.044

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