rs1143683

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000632.4(ITGAM):c.2573C>T(p.Ala858Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 1,613,704 control chromosomes in the GnomAD database, including 20,815 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.16 ( 2230 hom., cov: 31)

Exomes 𝑓: 0.15 ( 18585 hom. )

Consequence

ITGAM
NM_000632.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0680

Variant links:

Genes affected

ITGAM (HGNC:6149): (integrin subunit alpha M) This gene encodes the integrin alpha M chain. Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain. This I-domain containing alpha integrin combines with the beta 2 chain (ITGB2) to form a leukocyte-specific integrin referred to as macrophage receptor 1 ('Mac-1'), or inactivated-C3b (iC3b) receptor 3 ('CR3'). The alpha M beta 2 integrin is important in the adherence of neutrophils and monocytes to stimulated endothelium, and also in the phagocytosis of complement coated particles. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2009]

ITGAM links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006079823).

BP6

Variant 16-31325567-C-T is Benign according to our data. Variant chr16-31325567-C-T is described in ClinVar as [Benign]. Clinvar id is 1164968.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-31325567-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGAM	NM_000632.4 link	c.2573C>T	p.Ala858Val	missense_variant	Exon 21 of 30	ENST00000544665.9	NP_000623.2	P11215-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ITGAM	ENST00000544665.9 link	c.2573C>T	p.Ala858Val	missense_variant	Exon 21 of 30	1	NM_000632.4	ENSP00000441691.3	P11215-1
ITGAM	ENST00000648685.1 link	c.2576C>T	p.Ala859Val	missense_variant	Exon 21 of 30			ENSP00000496959.1	P11215-2
ITGAM	ENST00000561838.1 link	n.389C>T		non_coding_transcript_exon_variant	Exon 4 of 5	4

Frequencies

GnomAD3 genomes

AF:

0.164

AC:

24910

AN:

151958

Hom.:

2230

Cov.:

show subpopulations

Gnomad AFR

AF:

0.185

Gnomad AMI

AF:

0.191

Gnomad AMR

AF:

0.148

Gnomad ASJ

AF:

0.251

Gnomad EAS

AF:

0.0145

Gnomad SAS

AF:

0.249

Gnomad FIN

AF:

0.128

Gnomad MID

AF:

0.247

Gnomad NFE

AF:

0.160

Gnomad OTH

AF:

0.186

GnomAD2 exomes

AF:

0.157

AC:

39170

AN:

249184

AF XY:

0.165

show subpopulations

Gnomad AFR exome

AF:

0.191

Gnomad AMR exome

AF:

0.103

Gnomad ASJ exome

AF:

0.241

Gnomad EAS exome

AF:

0.0117

Gnomad FIN exome

AF:

0.126

Gnomad NFE exome

AF:

0.164

Gnomad OTH exome

AF:

0.171

GnomAD4 exome

AF:

0.153

AC:

223600

AN:

1461626

Hom.:

18585

Cov.:

AF XY:

0.157

AC XY:

114124

AN XY:

727098

show subpopulations

Gnomad4 AFR exome

AF:

0.190

AC:

6355

AN:

33474

Gnomad4 AMR exome

AF:

0.109

AC:

4888

AN:

44722

Gnomad4 ASJ exome

AF:

0.244

AC:

6381

AN:

26132

Gnomad4 EAS exome

AF:

0.00499

AC:

198

AN:

39698

Gnomad4 SAS exome

AF:

0.251

AC:

21638

AN:

86250

Gnomad4 FIN exome

AF:

0.126

AC:

6742

AN:

53402

Gnomad4 NFE exome

AF:

0.149

AC:

165949

AN:

1111812

Gnomad4 Remaining exome

AF:

0.166

AC:

9991

AN:

60368

Heterozygous variant carriers

10203

20405

30608

40810

51013

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

5844

11688

17532

23376

29220

<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:

0.164

AC:

24925

AN:

152078

Hom.:

2230

Cov.:

AF XY:

0.163

AC XY:

12150

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.185

AC:

0.184815

AN:

0.184815

Gnomad4 AMR

AF:

0.148

AC:

0.147702

AN:

0.147702

Gnomad4 ASJ

AF:

0.251

AC:

0.251153

AN:

0.251153

Gnomad4 EAS

AF:

0.0141

AC:

0.0141309

AN:

0.0141309

Gnomad4 SAS

AF:

0.249

AC:

0.249169

AN:

0.249169

Gnomad4 FIN

AF:

0.128

AC:

0.12814

AN:

0.12814

Gnomad4 NFE

AF:

0.160

AC:

0.159772

AN:

0.159772

Gnomad4 OTH

AF:

0.187

AC:

0.187027

AN:

0.187027

Heterozygous variant carriers

1011

2022

3033

4044

5055

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

272

544

816

1088

1360

<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:

0.164

Hom.:

8365

Bravo

AF:

0.163

TwinsUK

AF:

0.147

AC:

544

ALSPAC

AF:

0.142

AC:

548

ESP6500AA

AF:

0.177

AC:

716

ESP6500EA

AF:

0.159

AC:

1324

ExAC

AF:

0.163

AC:

19651

Asia WGS

AF:

0.137

AC:

476

AN:

3478

EpiCase

AF:

0.174

EpiControl

AF:

0.177

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

ITGAM-related disorder

Benign:1

Nov 12, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.71

CADD

Benign

2.8

DANN

Benign

0.72

DEOGEN2

Benign

0.028

.;.;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.42

.;T;T

MetaRNN

Benign

0.0061

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

.;.;L

PrimateAI

Benign

0.25

PROVEAN

Benign

-1.3

.;N;N

REVEL

Benign

0.043

Sift

Benign

0.14

.;T;T

Sift4G

Benign

0.55

.;T;T

Polyphen

0.0010

.;.;B

Vest4

0.016, 0.020

MPC

0.30

ClinPred

0.0013

GERP RS

-1.5

Varity_R

0.025

gMVP

0.21

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

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