rs2447859

Variant names:

• chr5-52882224-G-A
• rs2447859
• NM_181501.2:c.773+203G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_181501.2(ITGA1):​c.773+203G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 151,922 control chromosomes in the GnomAD database, including 2,967 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 0.19 (2967 hom., cov: 32)
• Consequence: ITGA1 NM_181501.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.183
• Publications: 7 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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGA1	NM_181501.2	c.773+203G>A		intron_variant	Intron 7 of 28	ENST00000282588.7	NP_852478.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGA1	ENST00000282588.7	c.773+203G>A		intron_variant	Intron 7 of 28	1	NM_181501.2	ENSP00000282588.5
ITGA1	ENST00000509049.1	n.389+203G>A		intron_variant	Intron 3 of 3	5
ITGA1	ENST00000513737.5	n.524+203G>A		intron_variant	Intron 5 of 5	5
ITGA1	ENST00000650673.1	n.773+203G>A		intron_variant	Intron 7 of 28			ENSP00000498529.1

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29327 AN: 151804 Hom.: 2955 Cov.: 32

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.248

Gnomad SAS AF: 0.279

Gnomad FIN AF: 0.158

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.197

Gnomad OTH AF: 0.177

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

GnomAD4 genome AF: 0.193 AC: 29381 AN: 151922 Hom.: 2967 Cov.: 32 AF XY: 0.191 AC XY: 14181 AN XY: 74218

African (AFR) AF: 0.204 AC: 8432 AN: 41430

American (AMR) AF: 0.136 AC: 2082 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 629 AN: 3460

East Asian (EAS) AF: 0.249 AC: 1288 AN: 5170

South Asian (SAS) AF: 0.277 AC: 1334 AN: 4812

European-Finnish (FIN) AF: 0.158 AC: 1663 AN: 10528

Middle Eastern (MID) AF: 0.190 AC: 55 AN: 290

European-Non Finnish (NFE) AF: 0.197 AC: 13383 AN: 67934

Other (OTH) AF: 0.179 AC: 378 AN: 2112

Alfa AF: 0.196 Hom.: 9344

Bravo AF: 0.190

Asia WGS AF: 0.246 AC: 851 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.58
DANN	Benign	0.21
PhyloP100		0.18
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: rs2447859; hg19: chr5-52178056;