NM_003638.3:c.2983-132A>G

Variant names:

• chr10-15519544-T-C
• rs7077361
• NM_003638.3:c.2983-132A>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.2983-132A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 939,584 control chromosomes in the GnomAD database, including 6,396 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 0.10 (916 hom., cov: 32)
  • Exomes 𝑓: 0.11 (5480 hom.)
• Consequence: ITGA8 NM_003638.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.72
• Publications: 28 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGA8	NM_003638.3	c.2983-132A>G		intron_variant	Intron 28 of 29	ENST00000378076.4	NP_003629.2
ITGA8	NM_001291494.2	c.2938-132A>G		intron_variant	Intron 27 of 28		NP_001278423.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGA8	ENST00000378076.4	c.2983-132A>G		intron_variant	Intron 28 of 29	1	NM_003638.3	ENSP00000367316.3

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15894 AN: 152038 Hom.: 918 Cov.: 32

Gnomad AFR AF: 0.0862

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.0720

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.0854

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.0980

GnomAD4 exome AF: 0.112 AC: 88380 AN: 787428 Hom.: 5480 AF XY: 0.112 AC XY: 46659 AN XY: 415034

African (AFR) AF: 0.0879 AC: 1671 AN: 19014

American (AMR) AF: 0.0543 AC: 1736 AN: 31958

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 2657 AN: 20286

East Asian (EAS) AF: 0.00236 AC: 85 AN: 36092

South Asian (SAS) AF: 0.0947 AC: 6256 AN: 66038

European-Finnish (FIN) AF: 0.124 AC: 5268 AN: 42382

Middle Eastern (MID) AF: 0.177 AC: 487 AN: 2750

European-Non Finnish (NFE) AF: 0.124 AC: 66099 AN: 531092

Other (OTH) AF: 0.109 AC: 4121 AN: 37816

GnomAD4 genome AF: 0.104 AC: 15894 AN: 152156 Hom.: 916 Cov.: 32 AF XY: 0.104 AC XY: 7702 AN XY: 74382

African (AFR) AF: 0.0862 AC: 3578 AN: 41524

American (AMR) AF: 0.0720 AC: 1100 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 464 AN: 3470

East Asian (EAS) AF: 0.00213 AC: 11 AN: 5174

South Asian (SAS) AF: 0.0855 AC: 412 AN: 4820

European-Finnish (FIN) AF: 0.132 AC: 1398 AN: 10572

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.126 AC: 8537 AN: 68000

Other (OTH) AF: 0.0974 AC: 206 AN: 2114

Alfa AF: 0.118 Hom.: 3368

Bravo AF: 0.101

Asia WGS AF: 0.0370 AC: 129 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.086
DANN	Benign	0.39
PhyloP100		-1.7
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: rs7077361; hg19: chr10-15561543;