rs3111397

Variant names:

• chr2-160194852-C-T
• rs3111397
• NM_000888.5:c.593+517G>A

Variant summary

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

The NM_000888.5(ITGB6):​c.593+517G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.78 in 152,122 control chromosomes in the GnomAD database, including 46,498 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 0.78 (46498 hom., cov: 32)
• Consequence: ITGB6 NM_000888.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.800
• Publications: 7 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.846 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000888.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGB6	NM_000888.5	MANE Select	c.593+517G>A		intron	N/A	NP_000879.2
	ITGB6	NM_001282353.2		c.593+517G>A		intron	N/A	NP_001269282.1
	ITGB6	NM_001282388.2		c.467+517G>A		intron	N/A	NP_001269317.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGB6	ENST00000283249.7	TSL:1 MANE Select	c.593+517G>A		intron	N/A	ENSP00000283249.2
	ITGB6	ENST00000409872.1	TSL:1	c.593+517G>A		intron	N/A	ENSP00000386367.1
	ITGB6	ENST00000428609.6	TSL:2	c.467+517G>A		intron	N/A	ENSP00000408024.2

Frequencies

GnomAD3 genomes AF: 0.780 AC: 118513 AN: 152004 Hom.: 46466 Cov.: 32

Gnomad AFR AF: 0.780

Gnomad AMI AF: 0.882

Gnomad AMR AF: 0.642

Gnomad ASJ AF: 0.767

Gnomad EAS AF: 0.807

Gnomad SAS AF: 0.868

Gnomad FIN AF: 0.819

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.796

Gnomad OTH AF: 0.768

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

GnomAD4 genome AF: 0.780 AC: 118585 AN: 152122 Hom.: 46498 Cov.: 32 AF XY: 0.780 AC XY: 57991 AN XY: 74358

African (AFR) AF: 0.779 AC: 32285 AN: 41426

American (AMR) AF: 0.641 AC: 9795 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.767 AC: 2661 AN: 3470

East Asian (EAS) AF: 0.808 AC: 4185 AN: 5180

South Asian (SAS) AF: 0.867 AC: 4183 AN: 4822

European-Finnish (FIN) AF: 0.819 AC: 8682 AN: 10602

Middle Eastern (MID) AF: 0.861 AC: 253 AN: 294

European-Non Finnish (NFE) AF: 0.796 AC: 54111 AN: 68018

Other (OTH) AF: 0.770 AC: 1626 AN: 2112

Alfa AF: 0.786 Hom.: 120623

Bravo AF: 0.763

Asia WGS AF: 0.835 AC: 2900 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.45
DANN	Benign	0.34
PhyloP100		-0.80
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: rs3111397; hg19: chr2-161051363;