chr12-53192471-G-A

Position:

• chr12-53192471-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

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 same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.0087 (5 hom., cov: 32)
  • Exomes 𝑓: 0.012 (119 hom.)
• Consequence: ITGB7 NM_000889.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.393

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]

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]

ACMG classification

Verdict is Benign. Variant got -10 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_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGB7	ENST00000267082.10	c.2014C>T	p.His672Tyr	missense_variant	14/16	1	NM_000889.3	P1
ZNF740	ENST00000416904.5	c.*4881G>A		3_prime_UTR_variant	7/7	1	NM_001004304.4	P1

Frequencies

GnomAD3 genomes AF: 0.00870 AC: 1324 AN: 152186 Hom.: 5 Cov.: 32

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.: 8 AF XY: 0.00883 AC XY: 1198 AN XY: 135644

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.: 31 AF XY: 0.0116 AC XY: 8452 AN XY: 727240

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.: 5 Cov.: 32 AF XY: 0.00815 AC XY: 607 AN XY: 74474

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.: 19

Bravo AF: 0.00832

TwinsUK AF: 0.0156 AC: 58

ALSPAC AF: 0.0135 AC: 52

ESP6500AA AF: 0.00182 AC: 8

ESP6500EA AF: 0.0134 AC: 115

ExAC AF: 0.00854 AC: 1037

Asia WGS AF: 0.00260 AC: 9 AN: 3478

EpiCase AF: 0.0132

EpiControl AF: 0.0129

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 21, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	15
DANN	Benign	0.94
DEOGEN2	Benign	0.27	T;T;.
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.30	N
MetaRNN	Benign	0.0045	T;T;T
MetaSVM	Uncertain	-0.059	T
MutationAssessor	Benign	1.2	L;L;.
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.46	T
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	T
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

Other links and lift over

dbSNP: rs11539433; hg19: chr12-53586255;