chr10-15531206-T-C

Position:

• chr10-15531206-T-C

Variant summary

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

The NM_003638.3(ITGA8):​c.2881-55A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 897,212 control chromosomes in the GnomAD database, including 17,883 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.18 (2576 hom., cov: 32)
  • Exomes 𝑓: 0.20 (15307 hom.)
• Consequence: ITGA8 NM_003638.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.543

Genes affected

ITGA8 (HGNC:6144): (integrin subunit alpha 8) Integrins are heterodimeric transmembrane receptor proteins that mediate numerous cellular processes including cell adhesion, cytoskeletal rearrangement, and activation of cell signaling pathways. Integrins are composed of alpha and beta subunits. This gene encodes the alpha 8 subunit of the heterodimeric integrin alpha8beta1 protein. The encoded protein is a single-pass type 1 membrane protein that contains multiple FG-GAP repeats. This repeat is predicted to fold into a beta propeller structure. This gene regulates the recruitment of mesenchymal cells into epithelial structures, mediates cell-cell interactions, and regulates neurite outgrowth of sensory and motor neurons. The integrin alpha8beta1 protein thus plays an important role in wound-healing and organogenesis. Mutations in this gene have been associated with renal hypodysplasia/aplasia-1 (RHDA1) and with several animal models of chronic kidney disease. Alternate splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Apr 2014]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 10-15531206-T-C is Benign according to our data. Variant chr10-15531206-T-C is described in ClinVar as [Benign]. Clinvar id is 1237225.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.196 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGA8	NM_003638.3	c.2881-55A>G		intron_variant		ENST00000378076.4	NP_003629.2
ITGA8	NM_001291494.2	c.2836-55A>G		intron_variant			NP_001278423.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGA8	ENST00000378076.4	c.2881-55A>G		intron_variant		1	NM_003638.3	ENSP00000367316	P1

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26750 AN: 152030 Hom.: 2577 Cov.: 32

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.167

GnomAD4 exome AF: 0.201 AC: 149987 AN: 745064 Hom.: 15307 AF XY: 0.200 AC XY: 75324 AN XY: 377386

Gnomad4 AFR exome AF: 0.105

Gnomad4 AMR exome AF: 0.229

Gnomad4 ASJ exome AF: 0.188

Gnomad4 EAS exome AF: 0.169

Gnomad4 SAS exome AF: 0.149

Gnomad4 FIN exome AF: 0.303

Gnomad4 NFE exome AF: 0.202

Gnomad4 OTH exome AF: 0.182

GnomAD4 genome AF: 0.176 AC: 26762 AN: 152148 Hom.: 2576 Cov.: 32 AF XY: 0.179 AC XY: 13317 AN XY: 74354

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.199

Gnomad4 ASJ AF: 0.185

Gnomad4 EAS AF: 0.143

Gnomad4 SAS AF: 0.144

Gnomad4 FIN AF: 0.300

Gnomad4 NFE AF: 0.199

Gnomad4 OTH AF: 0.169

Alfa AF: 0.189 Hom.: 2724

Bravo AF: 0.164

Asia WGS AF: 0.155 AC: 537 AN: 3474

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 20, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.8
DANN	Benign	0.84

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: rs9333240; hg19: chr10-15573205; COSMIC: COSV65230701;