chr12-53192752-C-T

Position:

• chr12-53192752-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.44

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 -14 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_single_submitter, 1 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	c.1885G>A	p.Gly629Ser	missense_variant	13/16	ENST00000267082.10
ZNF740	NM_001004304.4	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	c.1885G>A	p.Gly629Ser	missense_variant	13/16	1	NM_000889.3	P1
ZNF740	ENST00000416904.5	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.: 11 Cov.: 32

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.: 42 AF XY: 0.00959 AC XY: 1302 AN XY: 135760

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.: 80 Cov.: 32 AF XY: 0.00544 AC XY: 3957 AN XY: 727242

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.: 11 Cov.: 32 AF XY: 0.00710 AC XY: 529 AN XY: 74496

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.: 2

Bravo AF: 0.00471

TwinsUK AF: 0.00297 AC: 11

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.000681 AC: 3

ESP6500EA AF: 0.00291 AC: 25

ExAC AF: 0.00818 AC: 993

Asia WGS AF: 0.0110 AC: 38 AN: 3478

EpiCase AF: 0.00262

EpiControl AF: 0.00172

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

Mar 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Uncertain	0.060
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.73	D;D
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.88	D
MetaRNN	Benign	0.011	T;T
MetaSVM	Uncertain	0.32	D
MutationAssessor	Pathogenic	3.0	M;M
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.51	T
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	T
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

Other links and lift over

dbSNP: rs61754162; hg19: chr12-53586536; COSMIC: COSV57239218; COSMIC: COSV57239218;