rs2925757

Variant names:

• chr2-160244658-G-A
• rs2925757
• ENST00000485635.2:n.-567+27062C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000485635.2(ITGB6):​n.-567+27062C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.84 in 152,148 control chromosomes in the GnomAD database, including 53,845 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.84 (53845 hom., cov: 31)
• Consequence: ITGB6 ENST00000485635.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.64
• Publications: 14 publications found

Genes affected

ITGB6 (HGNC:6161): (integrin subunit beta 6) 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 a dimer with an alpha v chain and this heterodimer can bind to ligands like fibronectin and transforming growth factor beta 1. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

ITGB6 Gene-Disease associations (from GenCC):

• amelogenesis imperfecta type 1H

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• amelogenesis imperfecta type 1

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• amelogenesis imperfecta, type 3A

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.864 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGB6	ENST00000485635.2	n.-567+27062C>T		intron_variant	Intron 1 of 9	2		ENSP00000520446.1
ITGB6	ENST00000498478.1	n.260+8932C>T		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.840 AC: 127731 AN: 152030 Hom.: 53790 Cov.: 31

Gnomad AFR AF: 0.872

Gnomad AMI AF: 0.800

Gnomad AMR AF: 0.869

Gnomad ASJ AF: 0.755

Gnomad EAS AF: 0.867

Gnomad SAS AF: 0.808

Gnomad FIN AF: 0.861

Gnomad MID AF: 0.848

Gnomad NFE AF: 0.817

Gnomad OTH AF: 0.824

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.840 AC: 127839 AN: 152148 Hom.: 53845 Cov.: 31 AF XY: 0.841 AC XY: 62588 AN XY: 74380

African (AFR) AF: 0.872 AC: 36187 AN: 41502

American (AMR) AF: 0.869 AC: 13284 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.755 AC: 2623 AN: 3472

East Asian (EAS) AF: 0.867 AC: 4492 AN: 5180

South Asian (SAS) AF: 0.808 AC: 3889 AN: 4814

European-Finnish (FIN) AF: 0.861 AC: 9119 AN: 10594

Middle Eastern (MID) AF: 0.844 AC: 248 AN: 294

European-Non Finnish (NFE) AF: 0.817 AC: 55529 AN: 67986

Other (OTH) AF: 0.825 AC: 1738 AN: 2106

Alfa AF: 0.831 Hom.: 36937

Bravo AF: 0.844

Asia WGS AF: 0.863 AC: 2997 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	17
DANN	Benign	0.84
PhyloP100		1.6

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2925757; hg19: chr2-161101169;