rs2456203

Positions:

• chr5-52883958-T-C
• chr5-52883958-T-G

Variant summary

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

The NM_181501.2(ITGA1):​c.773+1937T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 152,094 control chromosomes in the GnomAD database, including 3,120 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 0.20 (3120 hom., cov: 32)
• Consequence: ITGA1 NM_181501.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.151

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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGA1	NM_181501.2	c.773+1937T>C		intron_variant		ENST00000282588.7	NP_852478.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGA1	ENST00000282588.7	c.773+1937T>C		intron_variant		1	NM_181501.2	ENSP00000282588	P1
ITGA1	ENST00000650673.1	c.773+1937T>C		intron_variant, NMD_transcript_variant				ENSP00000498529
ITGA1	ENST00000513737.5	n.524+1937T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.197 AC: 29996 AN: 151974 Hom.: 3108 Cov.: 32

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.249

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.197

Gnomad NFE AF: 0.198

Gnomad OTH AF: 0.179

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

GnomAD4 genome AF: 0.198 AC: 30049 AN: 152094 Hom.: 3120 Cov.: 32 AF XY: 0.195 AC XY: 14521 AN XY: 74354

Gnomad4 AFR AF: 0.217

Gnomad4 AMR AF: 0.138

Gnomad4 ASJ AF: 0.181

Gnomad4 EAS AF: 0.251

Gnomad4 SAS AF: 0.278

Gnomad4 FIN AF: 0.157

Gnomad4 NFE AF: 0.198

Gnomad4 OTH AF: 0.181

Alfa AF: 0.201 Hom.: 404

Bravo AF: 0.195

Asia WGS AF: 0.247 AC: 858 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.1
DANN	Benign	0.72

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: rs2456203; hg19: chr5-52179790;