Genetic Variant ITGA1:p.Asp978Asn (chr5-52933964-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_181501.2(ITGA1):c.2932G>A(p.Asp978Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000148 in 1,348,964 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ITGA1
NM_181501.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.73

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.4108808).

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.2932G>A	p.Asp978Asn	missense	Exon 23 of 29	NP_852478.1	P56199
	ITGA2-AS1	NR_186583.1		n.354-1428C>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ITGA1	ENST00000282588.7	TSL:1 MANE Select	c.2932G>A	p.Asp978Asn	missense	Exon 23 of 29	ENSP00000282588.5	P56199
ITGA1	ENST00000504669.5	TSL:1	n.5607G>A		non_coding_transcript_exon	Exon 12 of 18
ITGA1	ENST00000506275.1	TSL:1	n.2813G>A		non_coding_transcript_exon	Exon 1 of 7

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

151624

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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

GnomAD2 exomes

AF:

0.00000457

AC:

AN:

218674

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000370

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.00000148

AC:

AN:

1348964

Hom.:

Cov.:

AF XY:

0.00000150

AC XY:

AN XY:

668710

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30352

American (AMR)

AF:

0.0000533

AC:

AN:

37520

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23750

East Asian (EAS)

AF:

0.00

AC:

AN:

35836

South Asian (SAS)

AF:

0.00

AC:

AN:

66660

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50172

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5406

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1044206

Other (OTH)

AF:

0.00

AC:

AN:

55062

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

151624

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74004

African (AFR)

AF:

0.00

AC:

AN:

41352

American (AMR)

AF:

0.00

AC:

AN:

15200

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10556

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67742

Other (OTH)

AF:

0.00

AC:

AN:

2082

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

Eigen

Benign

0.053

Eigen_PC

Benign

0.21

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.79

M_CAP

Benign

0.0089

MetaRNN

Benign

0.41

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.7

PhyloP100

1.7

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-1.4

REVEL

Benign

0.096

Sift

Benign

0.041

Sift4G

Benign

0.24

Polyphen

0.097

Vest4

0.088

MutPred

0.84

Gain of relative solvent accessibility (P = 0.1684)

MVP

0.66

MPC

0.14

ClinPred

0.51

GERP RS

4.9

Varity_R

0.086

gMVP

0.64

Mutation Taster

=96/4

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over