NM_000888.5:c.2102-790C>T

Variant names:

• chr2-160108635-G-A
• rs6432593
• NM_000888.5:c.2102-790C>T

Variant summary

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

The NM_000888.5(ITGB6):​c.2102-790C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.789 in 152,154 control chromosomes in the GnomAD database, including 48,289 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 0.79 (48289 hom., cov: 31)
• Consequence: ITGB6 NM_000888.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14
• Publications: 4 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.938 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGB6	NM_000888.5	c.2102-790C>T		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.2102-790C>T		intron_variant	Intron 13 of 14	1	NM_000888.5	ENSP00000283249.2

Frequencies

GnomAD3 genomes AF: 0.789 AC: 119890 AN: 152036 Hom.: 48230 Cov.: 31

Gnomad AFR AF: 0.946

Gnomad AMI AF: 0.559

Gnomad AMR AF: 0.814

Gnomad ASJ AF: 0.606

Gnomad EAS AF: 0.774

Gnomad SAS AF: 0.642

Gnomad FIN AF: 0.739

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.721

Gnomad OTH AF: 0.739

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

GnomAD4 genome AF: 0.789 AC: 120013 AN: 152154 Hom.: 48289 Cov.: 31 AF XY: 0.790 AC XY: 58722 AN XY: 74360

African (AFR) AF: 0.946 AC: 39299 AN: 41558

American (AMR) AF: 0.815 AC: 12453 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.606 AC: 2103 AN: 3472

East Asian (EAS) AF: 0.774 AC: 3998 AN: 5164

South Asian (SAS) AF: 0.641 AC: 3083 AN: 4808

European-Finnish (FIN) AF: 0.739 AC: 7822 AN: 10580

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.721 AC: 48996 AN: 67968

Other (OTH) AF: 0.740 AC: 1564 AN: 2114

Alfa AF: 0.736 Hom.: 178194

Bravo AF: 0.804

Asia WGS AF: 0.742 AC: 2584 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.12
DANN	Benign	0.49
PhyloP100		-1.1
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: rs6432593; hg19: chr2-160965146;