rs10497211

Variant names:

• chr2-160125285-C-G
• rs10497211
• NM_000888.5:c.1883+1094G>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.1883+1094G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0661 in 152,292 control chromosomes in the GnomAD database, including 379 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 0.066 (379 hom., cov: 33)
• Consequence: ITGB6 NM_000888.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.54
• Publications: 2 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0784 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGB6	NM_000888.5	c.1883+1094G>C		intron_variant	Intron 11 of 14	ENST00000283249.7	NP_000879.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGB6	ENST00000283249.7	c.1883+1094G>C		intron_variant	Intron 11 of 14	1	NM_000888.5	ENSP00000283249.2

Frequencies

GnomAD3 genomes AF: 0.0661 AC: 10060 AN: 152174 Hom.: 379 Cov.: 33

Gnomad AFR AF: 0.0471

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0798

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.0677

Gnomad FIN AF: 0.0348

Gnomad MID AF: 0.143

Gnomad NFE AF: 0.0802

Gnomad OTH AF: 0.0794

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

GnomAD4 genome AF: 0.0661 AC: 10061 AN: 152292 Hom.: 379 Cov.: 33 AF XY: 0.0648 AC XY: 4826 AN XY: 74474

African (AFR) AF: 0.0471 AC: 1956 AN: 41564

American (AMR) AF: 0.0797 AC: 1218 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 502 AN: 3472

East Asian (EAS) AF: 0.000965 AC: 5 AN: 5182

South Asian (SAS) AF: 0.0676 AC: 326 AN: 4824

European-Finnish (FIN) AF: 0.0348 AC: 369 AN: 10616

Middle Eastern (MID) AF: 0.140 AC: 41 AN: 292

European-Non Finnish (NFE) AF: 0.0802 AC: 5457 AN: 68030

Other (OTH) AF: 0.0786 AC: 166 AN: 2112

Alfa AF: 0.0696 Hom.: 50

Bravo AF: 0.0683

Asia WGS AF: 0.0450 AC: 156 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.22
DANN	Benign	0.37
PhyloP100		-1.5
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: rs10497211; hg19: chr2-160981796;