rs870992

Variant names:

• chr5-52897406-A-G
• rs870992
• NM_181501.2:c.1091-49A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 26 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181501.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA1	NM_181501.2	MANE Select	c.1091-49A>G		intron	N/A	NP_852478.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA1	ENST00000282588.7	TSL:1 MANE Select	c.1091-49A>G		intron	N/A	ENSP00000282588.5
	ITGA1	ENST00000650673.1		n.*253-49A>G		intron	N/A	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

GnomAD2 exomes AF: 0.0792 AC: 19048 AN: 240508 AF XY: 0.0806

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 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

African (AFR) AF: 0.0188 AC: 488 AN: 25968

American (AMR) AF: 0.0990 AC: 4295 AN: 43390

Ashkenazi Jewish (ASJ) AF: 0.0901 AC: 2133 AN: 23666

East Asian (EAS) AF: 0.0680 AC: 2582 AN: 37952

South Asian (SAS) AF: 0.0653 AC: 5090 AN: 77998

European-Finnish (FIN) AF: 0.0671 AC: 3405 AN: 50708

Middle Eastern (MID) AF: 0.169 AC: 848 AN: 5004

European-Non Finnish (NFE) AF: 0.0825 AC: 66958 AN: 811988

Other (OTH) AF: 0.0790 AC: 3884 AN: 49144

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

African (AFR) AF: 0.0203 AC: 845 AN: 41572

American (AMR) AF: 0.106 AC: 1624 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0948 AC: 329 AN: 3470

East Asian (EAS) AF: 0.0667 AC: 346 AN: 5186

South Asian (SAS) AF: 0.0617 AC: 298 AN: 4826

European-Finnish (FIN) AF: 0.0677 AC: 719 AN: 10614

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.0920 AC: 6254 AN: 67996

Other (OTH) AF: 0.0907 AC: 191 AN: 2106

Alfa AF: 0.0876 Hom.: 637

Bravo AF: 0.0697

Asia WGS AF: 0.0680 AC: 238 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.4
DANN	Benign	0.57
PhyloP100		-0.28
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: rs870992; hg19: chr5-52193237;