Variant 5-52945020-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_181501.2(ITGA1):c.3363C>A(p.Ser1121Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00793 in 1,611,348 control chromosomes in the GnomAD database, including 71 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0058 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0082 ( 66 hom. )

Consequence

ITGA1
NM_181501.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.165

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 Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005416006).

BP6

Variant 5-52945020-C-A is Benign according to our data. Variant chr5-52945020-C-A is described in ClinVar as [Benign]. Clinvar id is 720666.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-52945020-C-A is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAd4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGA1	NM_181501.2 linkuse as main transcript	c.3363C>A	p.Ser1121Arg	missense_variant	27/29	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.3363C>A	p.Ser1121Arg	missense_variant	27/29	1	NM_181501.2	ENSP00000282588	P1
ITGA2-AS1	ENST00000662246.1 linkuse as main transcript	n.231+3805G>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.00582

AC:

884

AN:

151998

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00184

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00124

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.00996

Gnomad FIN

AF:

0.0108

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00890

Gnomad OTH

AF:

0.00383

GnomAD3 exomes

AF:

0.00691

AC:

1733

AN:

250688

Hom.:

AF XY:

0.00702

AC XY:

952

AN XY:

135542

show subpopulations

Gnomad AFR exome

AF:

0.00161

Gnomad AMR exome

AF:

0.00191

Gnomad ASJ exome

AF:

0.00229

Gnomad EAS exome

AF:

0.00147

Gnomad SAS exome

AF:

0.00916

Gnomad FIN exome

AF:

0.0118

Gnomad NFE exome

AF:

0.00886

Gnomad OTH exome

AF:

0.00852

GnomAD4 exome

AF:

0.00816

AC:

11901

AN:

1459232

Hom.:

Cov.:

AF XY:

0.00833

AC XY:

6046

AN XY:

726080

show subpopulations

Gnomad4 AFR exome

AF:

0.00132

Gnomad4 AMR exome

AF:

0.00204

Gnomad4 ASJ exome

AF:

0.00230

Gnomad4 EAS exome

AF:

0.000808

Gnomad4 SAS exome

AF:

0.00978

Gnomad4 FIN exome

AF:

0.0120

Gnomad4 NFE exome

AF:

0.00882

Gnomad4 OTH exome

AF:

0.00615

GnomAD4 genome

AF:

0.00582

AC:

885

AN:

152116

Hom.:

Cov.:

AF XY:

0.00590

AC XY:

439

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.00183

Gnomad4 AMR

AF:

0.00124

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.0102

Gnomad4 FIN

AF:

0.0108

Gnomad4 NFE

AF:

0.00892

Gnomad4 OTH

AF:

0.00379

Alfa

AF:

0.00809

Hom.:

Bravo

AF:

0.00468

TwinsUK

AF:

0.0102

AC:

ALSPAC

AF:

0.00986

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00791

AC:

ExAC

AF:

0.00721

AC:

875

EpiCase

AF:

0.00796

EpiControl

AF:

0.00771

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 20, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.055

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.43

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.65

MetaRNN

Benign

0.0054

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

MutationTaster

Benign

0.86

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.81

REVEL

Benign

0.064

Sift

Benign

0.21

Sift4G

Uncertain

0.045

Polyphen

0.14

Vest4

0.22

MutPred

0.35

Loss of ubiquitination at K1124 (P = 0.0298);

MVP

0.50

MPC

0.18

ClinPred

0.027

GERP RS

0.42

Varity_R

0.074

gMVP

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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