Variant chr5-52939596-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_181501.2(ITGA1):c.3085A>G(p.Asn1029Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000872 in 1,604,994 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

ITGA1
NM_181501.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0190

Variant links:

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]

ITGA1 links:

ITGA2-AS1 (HGNC:40306): (ITGA2 antisense RNA 1)

ITGA2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07990521).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGA1	NM_181501.2 linkuse as main transcript	c.3085A>G	p.Asn1029Asp	missense_variant	25/29	ENST00000282588.7	NP_852478.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGA1	ENST00000282588.7 linkuse as main transcript	c.3085A>G	p.Asn1029Asp	missense_variant	25/29	1	NM_181501.2	ENSP00000282588	P1
ITGA2-AS1	ENST00000662246.1 linkuse as main transcript	n.232-7060T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000121

AC:

AN:

247694

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134080

show subpopulations

Gnomad AFR exome

AF:

0.0000619

Gnomad AMR exome

AF:

0.0000603

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000344

AC:

AN:

1452664

Hom.:

Cov.:

AF XY:

0.00000277

AC XY:

AN XY:

723316

show subpopulations

Gnomad4 AFR exome

AF:

0.0000302

Gnomad4 AMR exome

AF:

0.0000229

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000500

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152330

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000588

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000564

Hom.:

Bravo

AF:

0.000125

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 14, 2023

The c.3085A>G (p.N1029D) alteration is located in exon 25 (coding exon 25) of the ITGA1 gene. This alteration results from a A to G substitution at nucleotide position 3085, causing the asparagine (N) at amino acid position 1029 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Benign

0.73

DEOGEN2

Benign

0.066

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.052

LIST_S2

Benign

0.47

M_CAP

Benign

0.0098

MetaRNN

Benign

0.080

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

MutationTaster

Benign

1.0

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.1

REVEL

Benign

0.054

Sift

Benign

0.66

Sift4G

Benign

0.65

Polyphen

0.076

Vest4

0.075

MVP

0.39

MPC

0.17

ClinPred

0.042

GERP RS

0.30

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.14

gMVP

0.44

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over