chr2-160203673-A-G

Variant names:

• chr2-160203673-A-G
• rs4665162
• ENST00000485635.2:n.-356+2190T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000485635.2(ITGB6):​n.-356+2190T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 152,120 control chromosomes in the GnomAD database, including 8,739 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 0.30 (8739 hom., cov: 32)
• Consequence: ITGB6 ENST00000485635.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.764
• Publications: 6 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.415 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.-356+2190T>C		intron_variant	Intron 2 of 9	2		ENSP00000520446.1
ITGB6	ENST00000498478.1	n.261-2456T>C		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46246 AN: 152002 Hom.: 8738 Cov.: 32

Gnomad AFR AF: 0.0911

Gnomad AMI AF: 0.434

Gnomad AMR AF: 0.287

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.321

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.489

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.420

Gnomad OTH AF: 0.286

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

GnomAD4 genome AF: 0.304 AC: 46251 AN: 152120 Hom.: 8739 Cov.: 32 AF XY: 0.307 AC XY: 22812 AN XY: 74344

African (AFR) AF: 0.0908 AC: 3770 AN: 41522

American (AMR) AF: 0.287 AC: 4388 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.193 AC: 671 AN: 3468

East Asian (EAS) AF: 0.322 AC: 1664 AN: 5164

South Asian (SAS) AF: 0.211 AC: 1015 AN: 4814

European-Finnish (FIN) AF: 0.489 AC: 5171 AN: 10582

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.419 AC: 28511 AN: 67966

Other (OTH) AF: 0.286 AC: 606 AN: 2116

Alfa AF: 0.349 Hom.: 1381

Bravo AF: 0.281

Asia WGS AF: 0.301 AC: 1046 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	11
DANN	Benign	0.88
PhyloP100		-0.76

Splicing

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

Other links and lift over

dbSNP: rs4665162; hg19: chr2-161060184;