rs870992

Positions:

• chr5-52897406-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_181501.2(ITGA1):​c.1091-49A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0786 in 1,278,076 control chromosomes in the GnomAD database, including 4,247 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 0.071 (459 hom., cov: 32)
  • Exomes 𝑓: 0.080 (3788 hom.)
• Consequence: ITGA1 NM_181501.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.281

Genes affected

ITGA1 (HGNC:6134): (integrin subunit alpha 1) This gene encodes the alpha 1 subunit of integrin receptors. This protein heterodimerizes with the beta 1 subunit to form a cell-surface receptor for collagen and laminin. The heterodimeric receptor is involved in cell-cell adhesion and may play a role in inflammation and fibrosis. The alpha 1 subunit contains an inserted (I) von Willebrand factor type I domain which is thought to be involved in collagen binding. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGA1	NM_181501.2	c.1091-49A>G		intron_variant		ENST00000282588.7	NP_852478.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGA1	ENST00000282588.7	c.1091-49A>G		intron_variant		1	NM_181501.2	ENSP00000282588.5
ITGA1	ENST00000650673.1	n.*253-49A>G		intron_variant				ENSP00000498529.1

Frequencies

GnomAD3 genomes AF: 0.0707 AC: 10756 AN: 152140 Hom.: 458 Cov.: 32

Gnomad AFR AF: 0.0204

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.0948

Gnomad EAS AF: 0.0669

Gnomad SAS AF: 0.0617

Gnomad FIN AF: 0.0677

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.0920

Gnomad OTH AF: 0.0902

GnomAD3 exomes AF: 0.0792 AC: 19048 AN: 240508 Hom.: 839 AF XY: 0.0806 AC XY: 10487 AN XY: 130060

Gnomad AFR exome AF: 0.0195

Gnomad AMR exome AF: 0.0996

Gnomad ASJ exome AF: 0.0905

Gnomad EAS exome AF: 0.0693

Gnomad SAS exome AF: 0.0631

Gnomad FIN exome AF: 0.0676

Gnomad NFE exome AF: 0.0877

Gnomad OTH exome AF: 0.0955

GnomAD4 exome AF: 0.0797 AC: 89683 AN: 1125818 Hom.: 3788 Cov.: 15 AF XY: 0.0807 AC XY: 46410 AN XY: 575338

Gnomad4 AFR exome AF: 0.0188

Gnomad4 AMR exome AF: 0.0990

Gnomad4 ASJ exome AF: 0.0901

Gnomad4 EAS exome AF: 0.0680

Gnomad4 SAS exome AF: 0.0653

Gnomad4 FIN exome AF: 0.0671

Gnomad4 NFE exome AF: 0.0825

Gnomad4 OTH exome AF: 0.0790

GnomAD4 genome AF: 0.0706 AC: 10754 AN: 152258 Hom.: 459 Cov.: 32 AF XY: 0.0711 AC XY: 5293 AN XY: 74438

Gnomad4 AFR AF: 0.0203

Gnomad4 AMR AF: 0.106

Gnomad4 ASJ AF: 0.0948

Gnomad4 EAS AF: 0.0667

Gnomad4 SAS AF: 0.0617

Gnomad4 FIN AF: 0.0677

Gnomad4 NFE AF: 0.0920

Gnomad4 OTH AF: 0.0907

Alfa AF: 0.0877 Hom.: 421

Bravo AF: 0.0697

Asia WGS AF: 0.0680 AC: 238 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.4
DANN	Benign	0.57

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

Publications

LitVar

Other links and lift over

dbSNP: rs870992; hg19: chr5-52193237;