chr5-52789009-C-T

Variant names:

• chr5-52789009-C-T
• rs6867040
• NM_181501.2:c.61+595C>T

Variant summary

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

The NM_181501.2(ITGA1):​c.61+595C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 152,090 control chromosomes in the GnomAD database, including 5,395 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 0.26 (5395 hom., cov: 32)
• Consequence: ITGA1 NM_181501.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.342
• Publications: 8 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]

PELO (HGNC:8829): (pelota mRNA surveillance and ribosome rescue factor) This gene encodes a protein which contains a conserved nuclear localization signal. The encoded protein may have a role in spermatogenesis, cell cycle control, and in meiotic cell division. [provided by RefSeq, Jul 2008]

PELO-AS1 (HGNC:56263): (PELO antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.302 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA1	NM_181501.2	MANE Select	c.61+595C>T		intron	N/A	NP_852478.1
	PELO	NM_015946.5	MANE Select	c.-511+595C>T		intron	N/A	NP_057030.3
	PELO-AS1	NR_186446.1		n.196-3417G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA1	ENST00000282588.7	TSL:1 MANE Select	c.61+595C>T		intron	N/A	ENSP00000282588.5
	PELO	ENST00000274311.3	TSL:1 MANE Select	c.-511+595C>T		intron	N/A	ENSP00000274311.2
	PELO	ENST00000901259.1		c.-507+468C>T		intron	N/A	ENSP00000571318.1

Frequencies

GnomAD3 genomes AF: 0.257 AC: 39079 AN: 151972 Hom.: 5389 Cov.: 32

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.233

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.342

Gnomad EAS AF: 0.206

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.328

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.305

Gnomad OTH AF: 0.259

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

GnomAD4 genome AF: 0.257 AC: 39100 AN: 152090 Hom.: 5395 Cov.: 32 AF XY: 0.255 AC XY: 18941 AN XY: 74338

African (AFR) AF: 0.185 AC: 7664 AN: 41494

American (AMR) AF: 0.214 AC: 3272 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.342 AC: 1186 AN: 3468

East Asian (EAS) AF: 0.206 AC: 1063 AN: 5170

South Asian (SAS) AF: 0.183 AC: 880 AN: 4820

European-Finnish (FIN) AF: 0.328 AC: 3464 AN: 10560

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.305 AC: 20752 AN: 67968

Other (OTH) AF: 0.259 AC: 548 AN: 2112

Alfa AF: 0.283 Hom.: 7670

Bravo AF: 0.246

Asia WGS AF: 0.196 AC: 682 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	4.0
DANN	Benign	0.78
PhyloP100		-0.34
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: rs6867040; hg19: chr5-52084843;