rs2456206

Positions:

• chr5-52883287-C-T

Variant summary

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

The NM_181501.2(ITGA1):​c.773+1266C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 152,144 control chromosomes in the GnomAD database, including 2,281 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 0.16 (2281 hom., cov: 33)
• Consequence: ITGA1 NM_181501.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.355

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=-0.73).
• 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/exons	MANE	UniProt
ITGA1	NM_181501.2	c.773+1266C>T		intron_variant		ENST00000282588.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGA1	ENST00000282588.7	c.773+1266C>T		intron_variant		1	NM_181501.2	P1
ITGA1	ENST00000650673.1	c.773+1266C>T		intron_variant, NMD_transcript_variant
ITGA1	ENST00000513737.5	n.524+1266C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24653 AN: 152026 Hom.: 2282 Cov.: 33

Gnomad AFR AF: 0.0922

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.249

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.197

Gnomad OTH AF: 0.155

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

GnomAD4 genome AF: 0.162 AC: 24667 AN: 152144 Hom.: 2281 Cov.: 33 AF XY: 0.161 AC XY: 12003 AN XY: 74390

Gnomad4 AFR AF: 0.0924

Gnomad4 AMR AF: 0.128

Gnomad4 ASJ AF: 0.182

Gnomad4 EAS AF: 0.250

Gnomad4 SAS AF: 0.278

Gnomad4 FIN AF: 0.157

Gnomad4 NFE AF: 0.197

Gnomad4 OTH AF: 0.157

Alfa AF: 0.191 Hom.: 1446

Bravo AF: 0.155

Asia WGS AF: 0.236 AC: 819 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	7.8
DANN	Benign	0.76

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: rs2456206; hg19: chr5-52179119;