10-15548353-A-G

Position:

• chr10-15548353-A-G

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.2880+102T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0155 in 788,164 control chromosomes in the GnomAD database, including 1,041 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.055 (742 hom., cov: 32)
  • Exomes 𝑓: 0.0060 (299 hom.)
• Consequence: ITGA8 NM_003638.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.716

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=-1.03).
• BP6: Variant 10-15548353-A-G is Benign according to our data. Variant chr10-15548353-A-G is described in ClinVar as [Benign]. Clinvar id is 1239658.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGA8	NM_003638.3	c.2880+102T>C		intron_variant		ENST00000378076.4	NP_003629.2
ITGA8	NM_001291494.2	c.2835+102T>C		intron_variant			NP_001278423.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGA8	ENST00000378076.4	c.2880+102T>C		intron_variant		1	NM_003638.3	ENSP00000367316	P1

Frequencies

GnomAD3 genomes AF: 0.0549 AC: 8350 AN: 152046 Hom.: 742 Cov.: 32

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0239

Gnomad ASJ AF: 0.00260

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000750

Gnomad OTH AF: 0.0401

GnomAD4 exome AF: 0.00605 AC: 3847 AN: 636000 Hom.: 299 AF XY: 0.00516 AC XY: 1750 AN XY: 338992

Gnomad4 AFR exome AF: 0.196

Gnomad4 AMR exome AF: 0.0147

Gnomad4 ASJ exome AF: 0.00346

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000895

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000614

Gnomad4 OTH exome AF: 0.0142

GnomAD4 genome AF: 0.0549 AC: 8360 AN: 152164 Hom.: 742 Cov.: 32 AF XY: 0.0534 AC XY: 3971 AN XY: 74402

Gnomad4 AFR AF: 0.189

Gnomad4 AMR AF: 0.0239

Gnomad4 ASJ AF: 0.00260

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000750

Gnomad4 OTH AF: 0.0397

Alfa AF: 0.0400 Hom.: 60

Bravo AF: 0.0621

Asia WGS AF: 0.0130 AC: 46 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 20, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.76
DANN	Benign	0.16

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: rs9333230; hg19: chr10-15590352;