2-160107546-G-T

Position:

• chr2-160107546-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000888.5(ITGB6):​c.2268+133C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 749,822 control chromosomes in the GnomAD database, including 72,414 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.36 (11718 hom., cov: 31)
  • Exomes 𝑓: 0.44 (60696 hom.)
• Consequence: ITGB6 NM_000888.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.512

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 2-160107546-G-T is Benign according to our data. Variant chr2-160107546-G-T is described in ClinVar as [Benign]. Clinvar id is 1286112.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.483 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGB6	NM_000888.5	c.2268+133C>A		intron_variant		ENST00000283249.7	NP_000879.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGB6	ENST00000283249.7	c.2268+133C>A		intron_variant		1	NM_000888.5	ENSP00000283249	P1

Frequencies

GnomAD3 genomes AF: 0.362 AC: 54815 AN: 151548 Hom.: 11717 Cov.: 31

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.409

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.317

Gnomad EAS AF: 0.306

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.519

Gnomad MID AF: 0.334

Gnomad NFE AF: 0.488

Gnomad OTH AF: 0.346

GnomAD4 exome AF: 0.439 AC: 262380 AN: 598152 Hom.: 60696 AF XY: 0.434 AC XY: 136300 AN XY: 314320

Gnomad4 AFR exome AF: 0.129

Gnomad4 AMR exome AF: 0.316

Gnomad4 ASJ exome AF: 0.318

Gnomad4 EAS exome AF: 0.341

Gnomad4 SAS exome AF: 0.279

Gnomad4 FIN exome AF: 0.505

Gnomad4 NFE exome AF: 0.492

Gnomad4 OTH exome AF: 0.418

GnomAD4 genome AF: 0.361 AC: 54823 AN: 151670 Hom.: 11718 Cov.: 31 AF XY: 0.363 AC XY: 26916 AN XY: 74070

Gnomad4 AFR AF: 0.136

Gnomad4 AMR AF: 0.359

Gnomad4 ASJ AF: 0.317

Gnomad4 EAS AF: 0.306

Gnomad4 SAS AF: 0.280

Gnomad4 FIN AF: 0.519

Gnomad4 NFE AF: 0.488

Gnomad4 OTH AF: 0.346

Alfa AF: 0.414 Hom.: 1877

Bravo AF: 0.340

Asia WGS AF: 0.337 AC: 1171 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.5
DANN	Benign	0.49

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

Publications

LitVar

Other links and lift over

dbSNP: rs13009231; hg19: chr2-160964057;