rs11861251

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000632.4(ITGAM):c.1322T>C(p.Met441Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 1,607,880 control chromosomes in the GnomAD database, including 17,232 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 0.14 ( 1704 hom., cov: 32)

Exomes 𝑓: 0.14 ( 15528 hom. )

Consequence

ITGAM
NM_000632.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.55

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006170988).

BP6

Variant 16-31278075-T-C is Benign according to our data. Variant chr16-31278075-T-C is described in ClinVar as [Benign]. Clinvar id is 1168376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGAM	NM_000632.4 link	c.1322T>C	p.Met441Thr	missense_variant	Exon 12 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.1322T>C	p.Met441Thr	missense_variant	Exon 12 of 30	1	NM_000632.4	ENSP00000441691.3	P11215-1
ITGAM	ENST00000567031.1 link	c.310+1026T>C		intron_variant	Intron 3 of 4	1		ENSP00000454568.1	H3BMV4
ITGAM	ENST00000648685.1 link	c.1322T>C	p.Met441Thr	missense_variant	Exon 12 of 30			ENSP00000496959.1	P11215-2

Frequencies

GnomAD3 genomes

AF:

0.143

AC:

21690

AN:

151988

Hom.:

1705

Cov.:

show subpopulations

Gnomad AFR

AF:

0.187

Gnomad AMI

AF:

0.0844

Gnomad AMR

AF:

0.0953

Gnomad ASJ

AF:

0.0672

Gnomad EAS

AF:

0.00193

Gnomad SAS

AF:

0.0414

Gnomad FIN

AF:

0.131

Gnomad MID

AF:

0.149

Gnomad NFE

AF:

0.152

Gnomad OTH

AF:

0.116

GnomAD3 exomes

AF:

0.107

AC:

25496

AN:

238718

Hom.:

1665

AF XY:

0.105

AC XY:

13592

AN XY:

129346

show subpopulations

Gnomad AFR exome

AF:

0.186

Gnomad AMR exome

AF:

0.0597

Gnomad ASJ exome

AF:

0.0663

Gnomad EAS exome

AF:

0.00177

Gnomad SAS exome

AF:

0.0447

Gnomad FIN exome

AF:

0.129

Gnomad NFE exome

AF:

0.144

Gnomad OTH exome

AF:

0.112

GnomAD4 exome

AF:

0.140

AC:

203581

AN:

1455774

Hom.:

15528

Cov.:

AF XY:

0.137

AC XY:

99287

AN XY:

723502

show subpopulations

Gnomad4 AFR exome

AF:

0.190

Gnomad4 AMR exome

AF:

0.0640

Gnomad4 ASJ exome

AF:

0.0668

Gnomad4 EAS exome

AF:

0.000809

Gnomad4 SAS exome

AF:

0.0472

Gnomad4 FIN exome

AF:

0.129

Gnomad4 NFE exome

AF:

0.156

Gnomad4 OTH exome

AF:

0.130

GnomAD4 genome

AF:

0.143

AC:

21694

AN:

152106

Hom.:

1704

Cov.:

AF XY:

0.139

AC XY:

10365

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.186

Gnomad4 AMR

AF:

0.0951

Gnomad4 ASJ

AF:

0.0672

Gnomad4 EAS

AF:

0.00194

Gnomad4 SAS

AF:

0.0417

Gnomad4 FIN

AF:

0.131

Gnomad4 NFE

AF:

0.152

Gnomad4 OTH

AF:

0.114

Alfa

AF:

0.133

Hom.:

3053

Bravo

AF:

0.140

TwinsUK

AF:

0.165

AC:

613

ALSPAC

AF:

0.160

AC:

617

ESP6500AA

AF:

0.176

AC:

728

ESP6500EA

AF:

0.151

AC:

1270

ExAC

AF:

0.108

AC:

13059

Asia WGS

AF:

0.0620

AC:

215

AN:

3478

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

Oct 24, 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

0.065

BayesDel_addAF

Benign

-0.87

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.27

DANN

Benign

0.20

DEOGEN2

Benign

0.015

.;.;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0025

LIST_S2

Benign

0.26

.;T;T

MetaRNN

Benign

0.0062

T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-1.3

N;N;N

PrimateAI

Benign

0.35

PROVEAN

Benign

0.82

.;N;N

REVEL

Benign

0.011

Sift

Benign

0.76

.;T;T

Sift4G

Benign

0.65

.;T;T

Polyphen

0.0

.;.;B

Vest4

0.010, 0.012

MPC

0.33

ClinPred

0.000059

GERP RS

-0.078

Varity_R

0.048

gMVP

0.21

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