NM_003638.3:c.2881-220G>C

Variant names:

• chr10-15531371-C-G
• rs9333237
• NM_003638.3:c.2881-220G>C

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.2881-220G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 151,928 control chromosomes in the GnomAD database, including 2,813 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.19 (2813 hom., cov: 33)
• Consequence: ITGA8 NM_003638.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.978
• 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=-0.9).
• BP6: Variant 10-15531371-C-G is Benign according to our data. Variant chr10-15531371-C-G is described in ClinVar as Benign. ClinVar VariationId is 1232924.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.196 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.2881-220G>C		intron	N/A	NP_003629.2	P53708
	ITGA8	NM_001291494.2		c.2836-220G>C		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.2881-220G>C		intron	N/A	ENSP00000367316.3	P53708
	ITGA8	ENST00000882526.1		c.2881-11959G>C		intron	N/A	ENSP00000552585.1
	ITGA8	ENST00000967017.1		c.2836-11959G>C		intron	N/A	ENSP00000637076.1

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28581 AN: 151810 Hom.: 2812 Cov.: 33

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.203

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.299

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.175

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

GnomAD4 genome AF: 0.188 AC: 28597 AN: 151928 Hom.: 2813 Cov.: 33 AF XY: 0.191 AC XY: 14152 AN XY: 74234

African (AFR) AF: 0.151 AC: 6280 AN: 41456

American (AMR) AF: 0.202 AC: 3087 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.185 AC: 641 AN: 3468

East Asian (EAS) AF: 0.143 AC: 739 AN: 5174

South Asian (SAS) AF: 0.143 AC: 689 AN: 4802

European-Finnish (FIN) AF: 0.299 AC: 3149 AN: 10532

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.199 AC: 13506 AN: 67930

Other (OTH) AF: 0.176 AC: 372 AN: 2108

Alfa AF: 0.121 Hom.: 228

Bravo AF: 0.179

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	-0.90
CADD	Benign	3.9
DANN	Benign	0.25
PhyloP100		0.98
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: rs9333237; hg19: chr10-15573370;