rs28643277

Variant names:

• chr10-15558672-C-A
• rs28643277
• NM_003638.3:c.2638-470G>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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]

ITGA8 Gene-Disease associations (from GenCC):

• renal hypodysplasia/aplasia 1

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• bilateral renal agenesis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003638.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA8	NM_003638.3	MANE Select	c.2638-470G>T		intron	N/A	NP_003629.2
	ITGA8	NM_001291494.2		c.2593-470G>T		intron	N/A	NP_001278423.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA8	ENST00000378076.4	TSL:1 MANE Select	c.2638-470G>T		intron	N/A	ENSP00000367316.3

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

African (AFR) AF: 0.524 AC: 21638 AN: 41320

American (AMR) AF: 0.335 AC: 5100 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.356 AC: 1233 AN: 3462

East Asian (EAS) AF: 0.138 AC: 711 AN: 5160

South Asian (SAS) AF: 0.271 AC: 1302 AN: 4810

European-Finnish (FIN) AF: 0.443 AC: 4662 AN: 10526

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.356 AC: 24152 AN: 67920

Other (OTH) AF: 0.358 AC: 753 AN: 2102

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.033
DANN	Benign	0.44
PhyloP100		-0.94
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs28643277; hg19: chr10-15600671;