chr12-53192752-C-T

Variant names:

• chr12-53192752-C-T
• rs61754162
• NM_000889.3:c.1885G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.44
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 11 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000889.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGB7	NM_000889.3	MANE Select	c.1885G>A	p.Gly629Ser	missense	Exon 13 of 16	NP_000880.1	P26010-1
	ZNF740	NM_001004304.4	MANE Select	c.*5162C>T		3_prime_UTR	Exon 7 of 7	NP_001004304.1	Q8NDX6
	ITGB7	NM_001414156.1		c.1885G>A	p.Gly629Ser	missense	Exon 12 of 15	NP_001401085.1	P26010-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGB7	ENST00000267082.10	TSL:1 MANE Select	c.1885G>A	p.Gly629Ser	missense	Exon 13 of 16	ENSP00000267082.4	P26010-1
	ZNF740	ENST00000416904.5	TSL:1 MANE Select	c.*5162C>T		3_prime_UTR	Exon 7 of 7	ENSP00000409463.2	Q8NDX6
	ITGB7	ENST00000422257.7	TSL:5	c.1885G>A	p.Gly629Ser	missense	Exon 13 of 16	ENSP00000408741.3	P26010-1

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

GnomAD2 exomes AF: 0.00935 AC: 2349 AN: 251156 AF XY: 0.00959

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 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

African (AFR) AF: 0.000747 AC: 25 AN: 33478

American (AMR) AF: 0.0228 AC: 1019 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.000344 AC: 9 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0246 AC: 2123 AN: 86256

European-Finnish (FIN) AF: 0.0175 AC: 937 AN: 53408

Middle Eastern (MID) AF: 0.00485 AC: 28 AN: 5768

European-Non Finnish (NFE) AF: 0.00236 AC: 2626 AN: 1112012

Other (OTH) AF: 0.00447 AC: 270 AN: 60396

GnomAD4 genome AF: 0.00573 AC: 873 AN: 152346 Hom.: 11 Cov.: 32 AF XY: 0.00710 AC XY: 529 AN XY: 74496

African (AFR) AF: 0.00151 AC: 63 AN: 41588

American (AMR) AF: 0.0172 AC: 264 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5182

South Asian (SAS) AF: 0.0221 AC: 107 AN: 4832

European-Finnish (FIN) AF: 0.0193 AC: 205 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00315 AC: 214 AN: 68040

Other (OTH) AF: 0.00804 AC: 17 AN: 2114

Alfa AF: 0.00293 Hom.: 7

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.51	T
MetaRNN	Benign	0.011	T
MetaSVM	Uncertain	0.32	D
MutationAssessor	Pathogenic	3.0	M
PhyloP100		2.4
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-3.1	D
REVEL	Pathogenic	0.67
Sift	Benign	0.13	T
Sift4G	Benign	0.17	T
Polyphen		1.0	D
Vest4		0.37
MVP		0.94
MPC		0.98
ClinPred		0.027	T
GERP RS		5.1
PromoterAI		-0.020	Neutral
Varity_R		0.18
gMVP		0.60
Mutation Taster		=94/6	polymorphism (auto)

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

Other links and lift over

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