2-160108189-T-G

Variant names:

• chr2-160108189-T-G
• rs10497212
• NM_000888.5:c.2102-344A>C

Variant summary

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

The NM_000888.5(ITGB6):​c.2102-344A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 150,296 control chromosomes in the GnomAD database, including 2,735 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 0.18 (2735 hom., cov: 31)
• Consequence: ITGB6 NM_000888.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.19
• Publications: 13 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=-0.79).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.303 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGB6	NM_000888.5	c.2102-344A>C		intron_variant	Intron 13 of 14	ENST00000283249.7	NP_000879.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGB6	ENST00000283249.7	c.2102-344A>C		intron_variant	Intron 13 of 14	1	NM_000888.5	ENSP00000283249.2

Frequencies

GnomAD3 genomes AF: 0.178 AC: 26802 AN: 150180 Hom.: 2715 Cov.: 31

Gnomad AFR AF: 0.210

Gnomad AMI AF: 0.0787

Gnomad AMR AF: 0.310

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.165

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.0979

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.189

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

GnomAD4 genome AF: 0.179 AC: 26854 AN: 150296 Hom.: 2735 Cov.: 31 AF XY: 0.177 AC XY: 13017 AN XY: 73402

African (AFR) AF: 0.211 AC: 8529 AN: 40482

American (AMR) AF: 0.311 AC: 4690 AN: 15098

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 515 AN: 3458

East Asian (EAS) AF: 0.165 AC: 847 AN: 5140

South Asian (SAS) AF: 0.129 AC: 615 AN: 4762

European-Finnish (FIN) AF: 0.0979 AC: 1013 AN: 10352

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.150 AC: 10155 AN: 67712

Other (OTH) AF: 0.188 AC: 394 AN: 2096

Alfa AF: 0.134 Hom.: 783

Bravo AF: 0.199

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.3
DANN	Benign	0.76
PhyloP100		1.2
Mutation Taster		=100/0	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: rs10497212; hg19: chr2-160964700;