rs1143679

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 ENST00000648685.1(ITGAM):c.230G>A(p.Arg77His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 1,592,706 control chromosomes in the GnomAD database, including 8,785 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R77C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.11 ( 979 hom., cov: 31)

Exomes 𝑓: 0.10 ( 7806 hom. )

Consequence

ITGAM
ENST00000648685.1 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.52

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 made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0012870133).

BP6

Variant 16-31265490-G-A is Benign according to our data. Variant chr16-31265490-G-A is described in ClinVar as [Benign]. Clinvar id is 1164965.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGAM	NM_000632.4 link	c.230G>A	p.Arg77His	missense_variant	Exon 3 of 30	ENST00000544665.9	NP_000623.2	P11215-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGAM	ENST00000544665.9 link	c.230G>A	p.Arg77His	missense_variant	Exon 3 of 30	1	NM_000632.4	ENSP00000441691.3		P11215-1
ITGAM	ENST00000648685.1 link	c.230G>A	p.Arg77His	missense_variant	Exon 3 of 30			ENSP00000496959.1		P11215-2

Frequencies

GnomAD3 genomes

AF:

0.108

AC:

16424

AN:

152038

Hom.:

974

Cov.:

show subpopulations

Gnomad AFR

AF:

0.105

Gnomad AMI

AF:

0.191

Gnomad AMR

AF:

0.102

Gnomad ASJ

AF:

0.152

Gnomad EAS

AF:

0.00638

Gnomad SAS

AF:

0.0664

Gnomad FIN

AF:

0.118

Gnomad MID

AF:

0.174

Gnomad NFE

AF:

0.116

Gnomad OTH

AF:

0.139

GnomAD3 exomes

AF:

0.0967

AC:

21083

AN:

218036

Hom.:

1170

AF XY:

0.0975

AC XY:

11570

AN XY:

118716

show subpopulations

Gnomad AFR exome

AF:

0.101

Gnomad AMR exome

AF:

0.0749

Gnomad ASJ exome

AF:

0.137

Gnomad EAS exome

AF:

0.00454

Gnomad SAS exome

AF:

0.0686

Gnomad FIN exome

AF:

0.116

Gnomad NFE exome

AF:

0.117

Gnomad OTH exome

AF:

0.114

GnomAD4 exome

AF:

0.101

AC:

144937

AN:

1440550

Hom.:

7806

Cov.:

AF XY:

0.101

AC XY:

71936

AN XY:

715476

show subpopulations

Gnomad4 AFR exome

AF:

0.108

Gnomad4 AMR exome

AF:

0.0794

Gnomad4 ASJ exome

AF:

0.140

Gnomad4 EAS exome

AF:

0.00188

Gnomad4 SAS exome

AF:

0.0718

Gnomad4 FIN exome

AF:

0.115

Gnomad4 NFE exome

AF:

0.105

Gnomad4 OTH exome

AF:

0.108

GnomAD4 genome

AF:

0.108

AC:

16456

AN:

152156

Hom.:

979

Cov.:

AF XY:

0.108

AC XY:

8042

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.106

Gnomad4 AMR

AF:

0.102

Gnomad4 ASJ

AF:

0.152

Gnomad4 EAS

AF:

0.00620

Gnomad4 SAS

AF:

0.0675

Gnomad4 FIN

AF:

0.118

Gnomad4 NFE

AF:

0.116

Gnomad4 OTH

AF:

0.138

Alfa

AF:

0.117

Hom.:

2212

Bravo

AF:

0.106

TwinsUK

AF:

0.102

AC:

380

ALSPAC

AF:

0.0978

AC:

377

ESP6500AA

AF:

0.0912

AC:

375

ESP6500EA

AF:

0.113

AC:

958

ExAC

AF:

0.0922

AC:

11141

Asia WGS

AF:

0.0460

AC:

159

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

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

0.059

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.65

CADD

Benign

0.11

DANN

Benign

0.90

DEOGEN2

Benign

0.025

.;.;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.022

LIST_S2

Benign

0.055

.;T;T

MetaRNN

Benign

0.0013

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.060

N;N;N

PrimateAI

Benign

0.21

PROVEAN

Benign

-0.21

.;N;N

REVEL

Benign

0.057

Sift

Benign

0.39

.;T;T

Sift4G

Benign

0.31

.;T;T

Polyphen

0.0020

.;.;B

Vest4

0.059, 0.12

MPC

0.36

ClinPred

0.0045

GERP RS

-9.3

Varity_R

0.020

gMVP

0.36

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