rs926770238

Variant names:

• chr12-53191969-C-G
• rs926770238
• NM_000889.3:c.2206G>C

Your query was ambiguous. Multiple possible variants found:

• chr12-53191969-C-G
• chr12-53191969-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000889.3(ITGB7):​c.2206G>C​(p.Val736Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000011 in 1,460,214 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V736M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: ITGB7 NM_000889.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.50
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.2206G>C	p.Val736Leu	missense	Exon 15 of 16	NP_000880.1	P26010-1
	ZNF740	NM_001004304.4	MANE Select	c.*4379C>G		3_prime_UTR	Exon 7 of 7	NP_001004304.1	Q8NDX6
	ITGB7	NM_001414156.1		c.2206G>C	p.Val736Leu	missense	Exon 14 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.2206G>C	p.Val736Leu	missense	Exon 15 of 16	ENSP00000267082.4	P26010-1
	ZNF740	ENST00000416904.5	TSL:1 MANE Select	c.*4379C>G		3_prime_UTR	Exon 7 of 7	ENSP00000409463.2	Q8NDX6
	ITGB7	ENST00000422257.7	TSL:5	c.2206G>C	p.Val736Leu	missense	Exon 15 of 16	ENSP00000408741.3	P26010-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000110 AC: 16 AN: 1460214 Hom.: 0 Cov.: 31 AF XY: 0.00000964 AC XY: 7 AN XY: 726448

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 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: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51774

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

European-Non Finnish (NFE) AF: 0.0000135 AC: 15 AN: 1111992

Other (OTH) AF: 0.0000166 AC: 1 AN: 60382

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.83	T
M_CAP	Uncertain	0.18	D
MetaRNN	Uncertain	0.45	T
MetaSVM	Pathogenic	0.80	D
MutationAssessor	Uncertain	2.2	M
PhyloP100		2.5
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-1.2	N
REVEL	Uncertain	0.55
Sift	Benign	0.076	T
Sift4G	Benign	0.17	T
Polyphen		1.0	D
Vest4		0.33
MutPred		0.39		Loss of catalytic residue at V736 (P = 0.081)
MVP		0.94
MPC		0.34
ClinPred		0.85	D
GERP RS		4.9
Varity_R		0.18
gMVP		0.51
Mutation Taster		=73/27	polymorphism

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: rs926770238; hg19: chr12-53585753;