Genetic Variant ITGA1:c.1091-49A>G (chr5-52897406-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_181501.2(ITGA1):c.1091-49A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0786 in 1,278,076 control chromosomes in the GnomAD database, including 4,247 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 0.071 ( 459 hom., cov: 32)

Exomes 𝑓: 0.080 ( 3788 hom. )

Consequence

ITGA1
NM_181501.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.281

Publications

26 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.102 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.1091-49A>G		intron	N/A	NP_852478.1	P56199

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA1	ENST00000282588.7	TSL:1 MANE Select	c.1091-49A>G		intron	N/A	ENSP00000282588.5	P56199
	ITGA1	ENST00000650673.1		n.*253-49A>G		intron	N/A	ENSP00000498529.1	A0A494C0F7

Frequencies

GnomAD3 genomes

AF:

0.0707

AC:

10756

AN:

152140

Hom.:

458

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0204

Gnomad AMI

AF:

0.115

Gnomad AMR

AF:

0.106

Gnomad ASJ

AF:

0.0948

Gnomad EAS

AF:

0.0669

Gnomad SAS

AF:

0.0617

Gnomad FIN

AF:

0.0677

Gnomad MID

AF:

0.155

Gnomad NFE

AF:

0.0920

Gnomad OTH

AF:

0.0902

GnomAD2 exomes

AF:

0.0792

AC:

19048

AN:

240508

AF XY:

0.0806

show subpopulations

Gnomad AFR exome

AF:

0.0195

Gnomad AMR exome

AF:

0.0996

Gnomad ASJ exome

AF:

0.0905

Gnomad EAS exome

AF:

0.0693

Gnomad FIN exome

AF:

0.0676

Gnomad NFE exome

AF:

0.0877

Gnomad OTH exome

AF:

0.0955

GnomAD4 exome

AF:

0.0797

AC:

89683

AN:

1125818

Hom.:

3788

Cov.:

AF XY:

0.0807

AC XY:

46410

AN XY:

575338

show subpopulations

African (AFR)

AF:

0.0188

AC:

488

AN:

25968

American (AMR)

AF:

0.0990

AC:

4295

AN:

43390

Ashkenazi Jewish (ASJ)

AF:

0.0901

AC:

2133

AN:

23666

East Asian (EAS)

AF:

0.0680

AC:

2582

AN:

37952

South Asian (SAS)

AF:

0.0653

AC:

5090

AN:

77998

European-Finnish (FIN)

AF:

0.0671

AC:

3405

AN:

50708

Middle Eastern (MID)

AF:

0.169

AC:

848

AN:

5004

European-Non Finnish (NFE)

AF:

0.0825

AC:

66958

AN:

811988

Other (OTH)

AF:

0.0790

AC:

3884

AN:

49144

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

3879

7759

11638

15518

19397

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1958

3916

5874

7832

9790

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0706

AC:

10754

AN:

152258

Hom.:

459

Cov.:

AF XY:

0.0711

AC XY:

5293

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.0203

AC:

845

AN:

41572

American (AMR)

AF:

0.106

AC:

1624

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.0948

AC:

329

AN:

3470

East Asian (EAS)

AF:

0.0667

AC:

346

AN:

5186

South Asian (SAS)

AF:

0.0617

AC:

298

AN:

4826

European-Finnish (FIN)

AF:

0.0677

AC:

719

AN:

10614

Middle Eastern (MID)

AF:

0.146

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0920

AC:

6254

AN:

67996

Other (OTH)

AF:

0.0907

AC:

191

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

527

1054

1581

2108

2635

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

256

384

512

640

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0876

Hom.:

637

Bravo

AF:

0.0697

Asia WGS

AF:

0.0680

AC:

238

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.4

(source)

DANN

Benign

0.57

PhyloP100

-0.28

Mutation Taster

=100/0

polymorphism (auto)

(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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over