10-15548373-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003638.3(ITGA8):c.2880+82C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.979 in 942,970 control chromosomes in the GnomAD database, including 453,235 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.95 (69298 hom., cov: 32)
  • Exomes 𝑓: 0.98 (383937 hom.)
• Consequence: ITGA8 NM_003638.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.28

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BP6: Variant 10-15548373-G-T is Benign according to our data. Variant chr10-15548373-G-T is described in ClinVar as [Benign]. Clinvar id is 1250211.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.99 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITGA8	NM_003638.3	c.2880+82C>A		intron_variant		ENST00000378076.4
ITGA8	NM_001291494.2	c.2835+82C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGA8	ENST00000378076.4	c.2880+82C>A		intron_variant		1	NM_003638.3	P1

Frequencies

GnomAD3 genomes AF: 0.952 AC: 144848 AN: 152144 Hom.: 69254 Cov.: 32

Gnomad AFR AF: 0.871

Gnomad AMI AF: 0.988

Gnomad AMR AF: 0.981

Gnomad ASJ AF: 0.986

Gnomad EAS AF: 0.789

Gnomad SAS AF: 0.982

Gnomad FIN AF: 0.993

Gnomad MID AF: 0.994

Gnomad NFE AF: 0.996

Gnomad OTH AF: 0.958

GnomAD4 exome AF: 0.985 AC: 778617 AN: 790708 Hom.: 383937 AF XY: 0.985 AC XY: 409432 AN XY: 415510

Gnomad4 AFR exome AF: 0.871

Gnomad4 AMR exome AF: 0.990

Gnomad4 ASJ exome AF: 0.988

Gnomad4 EAS exome AF: 0.841

Gnomad4 SAS exome AF: 0.987

Gnomad4 FIN exome AF: 0.993

Gnomad4 NFE exome AF: 0.996

Gnomad4 OTH exome AF: 0.975

GnomAD4 genome AF: 0.952 AC: 144952 AN: 152262 Hom.: 69298 Cov.: 32 AF XY: 0.952 AC XY: 70909 AN XY: 74456

Gnomad4 AFR AF: 0.871

Gnomad4 AMR AF: 0.981

Gnomad4 ASJ AF: 0.986

Gnomad4 EAS AF: 0.790

Gnomad4 SAS AF: 0.982

Gnomad4 FIN AF: 0.993

Gnomad4 NFE AF: 0.996

Gnomad4 OTH AF: 0.959

Alfa AF: 0.970 Hom.: 8023

Bravo AF: 0.946

Asia WGS AF: 0.904 AC: 3145 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.087
Dann	Benign	0.35

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: rs9333229; hg19: chr10-15590372;