rs28643277

Positions:

• chr10-15558672-C-A
• chr10-15558672-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003638.3(ITGA8):​c.2638-470G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.395 in 151,742 control chromosomes in the GnomAD database, including 12,461 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.40 (12461 hom., cov: 32)
• Consequence: ITGA8 NM_003638.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.942

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.518 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITGA8	NM_003638.3	c.2638-470G>T		intron_variant		ENST00000378076.4
ITGA8	NM_001291494.2	c.2593-470G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGA8	ENST00000378076.4	c.2638-470G>T		intron_variant		1	NM_003638.3	P1

Frequencies

GnomAD3 genomes AF: 0.395 AC: 59905 AN: 151624 Hom.: 12456 Cov.: 32

Gnomad AFR AF: 0.524

Gnomad AMI AF: 0.326

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.356

Gnomad EAS AF: 0.137

Gnomad SAS AF: 0.270

Gnomad FIN AF: 0.443

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.358

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.395 AC: 59952 AN: 151742 Hom.: 12461 Cov.: 32 AF XY: 0.394 AC XY: 29203 AN XY: 74158

Gnomad4 AFR AF: 0.524

Gnomad4 AMR AF: 0.335

Gnomad4 ASJ AF: 0.356

Gnomad4 EAS AF: 0.138

Gnomad4 SAS AF: 0.271

Gnomad4 FIN AF: 0.443

Gnomad4 NFE AF: 0.356

Gnomad4 OTH AF: 0.358

Alfa AF: 0.226 Hom.: 477

Bravo AF: 0.392

Asia WGS AF: 0.222 AC: 772 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.033
DANN	Benign	0.44

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: rs28643277; hg19: chr10-15600671;