chr2-160130410-G-T

Variant names:

• chr2-160130410-G-T
• rs10497208
• NM_000888.5:c.1661-3809C>A

Variant summary

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

The ENST00000283249.7(ITGB6):​c.1661-3809C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.669 in 151,822 control chromosomes in the GnomAD database, including 34,337 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 0.67 (34337 hom., cov: 31)
• Consequence: ITGB6 ENST00000283249.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.864
• Publications: 1 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.726 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000283249.7. 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.1661-3809C>A		intron	N/A	NP_000879.2
	ITGB6	NM_001282353.2		c.1661-3809C>A		intron	N/A	NP_001269282.1
	ITGB6	NM_001282388.2		c.1535-3809C>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.1661-3809C>A		intron	N/A	ENSP00000283249.2
	ITGB6	ENST00000409872.1	TSL:1	c.1661-3809C>A		intron	N/A	ENSP00000386367.1
	ITGB6	ENST00000428609.6	TSL:2	c.1535-3809C>A		intron	N/A	ENSP00000408024.2

Frequencies

GnomAD3 genomes AF: 0.669 AC: 101481 AN: 151706 Hom.: 34298 Cov.: 31

Gnomad AFR AF: 0.668

Gnomad AMI AF: 0.522

Gnomad AMR AF: 0.737

Gnomad ASJ AF: 0.565

Gnomad EAS AF: 0.476

Gnomad SAS AF: 0.494

Gnomad FIN AF: 0.702

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.685

Gnomad OTH AF: 0.643

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

GnomAD4 genome AF: 0.669 AC: 101578 AN: 151822 Hom.: 34337 Cov.: 31 AF XY: 0.669 AC XY: 49615 AN XY: 74174

African (AFR) AF: 0.668 AC: 27657 AN: 41382

American (AMR) AF: 0.738 AC: 11250 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.565 AC: 1960 AN: 3472

East Asian (EAS) AF: 0.477 AC: 2462 AN: 5166

South Asian (SAS) AF: 0.494 AC: 2380 AN: 4816

European-Finnish (FIN) AF: 0.702 AC: 7368 AN: 10496

Middle Eastern (MID) AF: 0.524 AC: 153 AN: 292

European-Non Finnish (NFE) AF: 0.685 AC: 46524 AN: 67928

Other (OTH) AF: 0.641 AC: 1349 AN: 2106

Alfa AF: 0.579 Hom.: 1634

Bravo AF: 0.674

Asia WGS AF: 0.546 AC: 1890 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.2
DANN	Benign	0.79
PhyloP100		-0.86
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: rs10497208; hg19: chr2-160986921;