chr2-160101838-GA-G

Position:

• chr2-160101838-GA-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000888.5(ITGB6):​c.2269-5del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.57 (29163 hom., cov: 0)
  • Exomes 𝑓: 0.55 (96160 hom.)
  • Failed GnomAD Quality Control
• Consequence: ITGB6 NM_000888.5 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.917

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 2-160101838-GA-G is Benign according to our data. Variant chr2-160101838-GA-G is described in ClinVar as [Benign]. Clinvar id is 218475.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.76 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGB6	NM_000888.5	c.2269-5del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000283249.7	NP_000879.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGB6	ENST00000283249.7	c.2269-5del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_000888.5	ENSP00000283249	P1

Frequencies

GnomAD3 genomes AF: 0.571 AC: 85718 AN: 150220 Hom.: 29162 Cov.: 0

Gnomad AFR AF: 0.191

Gnomad AMI AF: 0.851

Gnomad AMR AF: 0.545

Gnomad ASJ AF: 0.710

Gnomad EAS AF: 0.539

Gnomad SAS AF: 0.618

Gnomad FIN AF: 0.770

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.765

Gnomad OTH AF: 0.603

GnomAD3 exomes AF: 0.509 AC: 82719 AN: 162560 Hom.: 14857 AF XY: 0.520 AC XY: 44878 AN XY: 86300

Gnomad AFR exome AF: 0.189

Gnomad AMR exome AF: 0.389

Gnomad ASJ exome AF: 0.531

Gnomad EAS exome AF: 0.443

Gnomad SAS exome AF: 0.488

Gnomad FIN exome AF: 0.613

Gnomad NFE exome AF: 0.598

Gnomad OTH exome AF: 0.529

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.549 AC: 529515 AN: 964114 Hom.: 96160 Cov.: 0 AF XY: 0.550 AC XY: 270894 AN XY: 492450

Gnomad4 AFR exome AF: 0.171

Gnomad4 AMR exome AF: 0.387

Gnomad4 ASJ exome AF: 0.538

Gnomad4 EAS exome AF: 0.445

Gnomad4 SAS exome AF: 0.498

Gnomad4 FIN exome AF: 0.591

Gnomad4 NFE exome AF: 0.579

Gnomad4 OTH exome AF: 0.529

GnomAD4 genome AF: 0.570 AC: 85714 AN: 150330 Hom.: 29163 Cov.: 0 AF XY: 0.571 AC XY: 41851 AN XY: 73308

Gnomad4 AFR AF: 0.191

Gnomad4 AMR AF: 0.544

Gnomad4 ASJ AF: 0.710

Gnomad4 EAS AF: 0.540

Gnomad4 SAS AF: 0.618

Gnomad4 FIN AF: 0.770

Gnomad4 NFE AF: 0.765

Gnomad4 OTH AF: 0.602

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia

Apr 17, 2015

- -

Amelogenesis imperfecta type 1H Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 09, 2021

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs5835793; hg19: chr2-160958349;