rs150955757

Variant names:

• chr12-53192490-G-A
• rs150955757
• NM_000889.3:c.1995C>T

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_000889.3(ITGB7):​c.1995C>T​(p.Asn665Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000296 in 1,614,204 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0016 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00016 (0 hom.)
• Consequence: ITGB7 NM_000889.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.14
• Publications: 0 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 -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 12-53192490-G-A is Benign according to our data. Variant chr12-53192490-G-A is described in ClinVar as Benign. ClinVar VariationId is 707897.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.14 with no splicing effect.

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.1995C>T	p.Asn665Asn	synonymous	Exon 14 of 16	NP_000880.1	P26010-1
	ZNF740	NM_001004304.4	MANE Select	c.*4900G>A		3_prime_UTR	Exon 7 of 7	NP_001004304.1	Q8NDX6
	ITGB7	NM_001414156.1		c.1995C>T	p.Asn665Asn	synonymous	Exon 13 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.1995C>T	p.Asn665Asn	synonymous	Exon 14 of 16	ENSP00000267082.4	P26010-1
	ZNF740	ENST00000416904.5	TSL:1 MANE Select	c.*4900G>A		3_prime_UTR	Exon 7 of 7	ENSP00000409463.2	Q8NDX6
	ITGB7	ENST00000422257.7	TSL:5	c.1995C>T	p.Asn665Asn	synonymous	Exon 14 of 16	ENSP00000408741.3	P26010-1

Frequencies

GnomAD3 genomes AF: 0.00162 AC: 247 AN: 152220 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00577

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.000955

GnomAD2 exomes AF: 0.000331 AC: 83 AN: 250504 AF XY: 0.000207

Gnomad AFR exome AF: 0.00469

Gnomad AMR exome AF: 0.000174

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000885

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000158 AC: 231 AN: 1461866 Hom.: 0 Cov.: 31 AF XY: 0.000132 AC XY: 96 AN XY: 727232

African (AFR) AF: 0.00529 AC: 177 AN: 33480

American (AMR) AF: 0.000246 AC: 11 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

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

South Asian (SAS) AF: 0.0000580 AC: 5 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1112010

Other (OTH) AF: 0.000546 AC: 33 AN: 60396

GnomAD4 genome AF: 0.00162 AC: 247 AN: 152338 Hom.: 0 Cov.: 32 AF XY: 0.00157 AC XY: 117 AN XY: 74486

African (AFR) AF: 0.00575 AC: 239 AN: 41574

American (AMR) AF: 0.000196 AC: 3 AN: 15298

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

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

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68044

Other (OTH) AF: 0.000945 AC: 2 AN: 2116

Alfa AF: 0.000643 Hom.: 0

Bravo AF: 0.00165

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.028
DANN	Benign	0.65
PhyloP100		-1.1
PromoterAI		0.023	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs150955757; hg19: chr12-53586274;