rs9333236

Variant names:

• chr10-15531415-T-C
• rs9333236
• NM_003638.3:c.2881-264A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003638.3(ITGA8):​c.2881-264A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 125,832 control chromosomes in the GnomAD database, including 2,806 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.23 (2806 hom., cov: 30)
• Consequence: ITGA8 NM_003638.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0130
• Publications: 1 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BP6: Variant 10-15531415-T-C is Benign according to our data. Variant chr10-15531415-T-C is described in ClinVar as Benign. ClinVar VariationId is 1279678.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.239 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA8	NM_003638.3	MANE Select	c.2881-264A>G		intron	N/A	NP_003629.2	P53708
	ITGA8	NM_001291494.2		c.2836-264A>G		intron	N/A	NP_001278423.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA8	ENST00000378076.4	TSL:1 MANE Select	c.2881-264A>G		intron	N/A	ENSP00000367316.3	P53708
	ITGA8	ENST00000882526.1		c.2881-12003A>G		intron	N/A	ENSP00000552585.1
	ITGA8	ENST00000967017.1		c.2836-12003A>G		intron	N/A	ENSP00000637076.1

Frequencies

GnomAD3 genomes AF: 0.227 AC: 28495 AN: 125758 Hom.: 2805 Cov.: 30

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.229

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.358

Gnomad MID AF: 0.153

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.210

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

GnomAD4 genome AF: 0.227 AC: 28510 AN: 125832 Hom.: 2806 Cov.: 30 AF XY: 0.229 AC XY: 14112 AN XY: 61654

African (AFR) AF: 0.188 AC: 6269 AN: 33346

American (AMR) AF: 0.227 AC: 3077 AN: 13542

Ashkenazi Jewish (ASJ) AF: 0.229 AC: 640 AN: 2800

East Asian (EAS) AF: 0.142 AC: 732 AN: 5154

South Asian (SAS) AF: 0.167 AC: 690 AN: 4136

European-Finnish (FIN) AF: 0.358 AC: 3134 AN: 8758

Middle Eastern (MID) AF: 0.145 AC: 32 AN: 220

European-Non Finnish (NFE) AF: 0.243 AC: 13464 AN: 55440

Other (OTH) AF: 0.211 AC: 370 AN: 1752

Alfa AF: 0.197 Hom.: 3861

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	7.7
DANN	Benign	0.35
PhyloP100		0.013
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs9333236; hg19: chr10-15573414;