chr2-160101949-A-T

Position:

• chr2-160101949-A-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.2269-115T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 638,084 control chromosomes in the GnomAD database, including 8,978 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (2607 hom., cov: 33)
  • Exomes 𝑓: 0.15 (6371 hom.)
• Consequence: ITGB6 NM_000888.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.200

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=-0.85).
• BP6: Variant 2-160101949-A-T is Benign according to our data. Variant chr2-160101949-A-T is described in ClinVar as [Benign]. Clinvar id is 1221702.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITGB6	NM_000888.5	c.2269-115T>A		intron_variant		ENST00000283249.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGB6	ENST00000283249.7	c.2269-115T>A		intron_variant		1	NM_000888.5	P1

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26434 AN: 152020 Hom.: 2589 Cov.: 33

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.0779

Gnomad AMR AF: 0.306

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.165

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.0975

Gnomad MID AF: 0.0860

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.188

GnomAD4 exome AF: 0.152 AC: 73941 AN: 485950 Hom.: 6371 AF XY: 0.149 AC XY: 38899 AN XY: 261216

Gnomad4 AFR exome AF: 0.196

Gnomad4 AMR exome AF: 0.375

Gnomad4 ASJ exome AF: 0.142

Gnomad4 EAS exome AF: 0.163

Gnomad4 SAS exome AF: 0.118

Gnomad4 FIN exome AF: 0.110

Gnomad4 NFE exome AF: 0.146

Gnomad4 OTH exome AF: 0.164

GnomAD4 genome AF: 0.174 AC: 26483 AN: 152134 Hom.: 2607 Cov.: 33 AF XY: 0.173 AC XY: 12874 AN XY: 74380

Gnomad4 AFR AF: 0.196

Gnomad4 AMR AF: 0.307

Gnomad4 ASJ AF: 0.148

Gnomad4 EAS AF: 0.165

Gnomad4 SAS AF: 0.127

Gnomad4 FIN AF: 0.0975

Gnomad4 NFE AF: 0.149

Gnomad4 OTH AF: 0.187

Alfa AF: 0.161 Hom.: 265

Bravo AF: 0.194

Asia WGS AF: 0.155 AC: 540 AN: 3476

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	-0.85
CADD	Benign	2.7
DANN	Benign	0.43

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: rs4078235; hg19: chr2-160958460;