chr10-15531338-G-C

Variant names:

• chr10-15531338-G-C
• rs9333239
• NM_003638.3:c.2881-187C>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.2881-187C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.943 in 151,854 control chromosomes in the GnomAD database, including 67,982 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.94 (67982 hom., cov: 30)
• Consequence: ITGA8 NM_003638.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.28
• 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=-1.01).
• BP6: Variant 10-15531338-G-C is Benign according to our data. Variant chr10-15531338-G-C is described in ClinVar as Benign. ClinVar VariationId is 1277160.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.993 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.2881-187C>G		intron	N/A	NP_003629.2	P53708
	ITGA8	NM_001291494.2		c.2836-187C>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.2881-187C>G		intron	N/A	ENSP00000367316.3	P53708
	ITGA8	ENST00000882526.1		c.2881-11926C>G		intron	N/A	ENSP00000552585.1
	ITGA8	ENST00000967017.1		c.2836-11926C>G		intron	N/A	ENSP00000637076.1

Frequencies

GnomAD3 genomes AF: 0.943 AC: 143112 AN: 151736 Hom.: 67937 Cov.: 30

Gnomad AFR AF: 0.836

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.975

Gnomad ASJ AF: 0.986

Gnomad EAS AF: 0.774

Gnomad SAS AF: 0.981

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.997

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.952

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

GnomAD4 genome AF: 0.943 AC: 143217 AN: 151854 Hom.: 67982 Cov.: 30 AF XY: 0.944 AC XY: 70013 AN XY: 74158

African (AFR) AF: 0.836 AC: 34569 AN: 41362

American (AMR) AF: 0.975 AC: 14879 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.986 AC: 3424 AN: 3472

East Asian (EAS) AF: 0.775 AC: 3984 AN: 5140

South Asian (SAS) AF: 0.982 AC: 4718 AN: 4806

European-Finnish (FIN) AF: 1.00 AC: 10520 AN: 10524

Middle Eastern (MID) AF: 0.997 AC: 293 AN: 294

European-Non Finnish (NFE) AF: 0.999 AC: 67911 AN: 67974

Other (OTH) AF: 0.953 AC: 2011 AN: 2110

Alfa AF: 0.967 Hom.: 8694

Bravo AF: 0.934

Asia WGS AF: 0.899 AC: 3127 AN: 3478

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	-1.0
CADD	Benign	0.47
DANN	Benign	0.52
PhyloP100		-2.3
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: rs9333239; hg19: chr10-15573337;