rs1143679

Variant names:

• chr16-31265490-G-A
• rs1143679
• NM_000632.4:c.230G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-31265490-G-A
• chr16-31265490-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000632.4(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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). 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 NM_000632.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.52
• Publications: 182 publications found

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 Gene-Disease associations (from GenCC):

• systemic lupus erythematosus

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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	c.230G>A	p.Arg77His	missense_variant	Exon 3 of 30	ENST00000544665.9	NP_000623.2

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16424 AN: 152038 Hom.: 974 Cov.: 31

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

GnomAD2 exomes AF: 0.0967 AC: 21083 AN: 218036 AF XY: 0.0975

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 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.: 29 AF XY: 0.101 AC XY: 71936 AN XY: 715476

African (AFR) AF: 0.108 AC: 3548 AN: 32900

American (AMR) AF: 0.0794 AC: 3293 AN: 41450

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 3576 AN: 25494

East Asian (EAS) AF: 0.00188 AC: 73 AN: 38922

South Asian (SAS) AF: 0.0718 AC: 5994 AN: 83512

European-Finnish (FIN) AF: 0.115 AC: 6019 AN: 52270

Middle Eastern (MID) AF: 0.154 AC: 882 AN: 5716

European-Non Finnish (NFE) AF: 0.105 AC: 115152 AN: 1100754

Other (OTH) AF: 0.108 AC: 6400 AN: 59532

GnomAD4 genome AF: 0.108 AC: 16456 AN: 152156 Hom.: 979 Cov.: 31 AF XY: 0.108 AC XY: 8042 AN XY: 74402

African (AFR) AF: 0.106 AC: 4387 AN: 41522

American (AMR) AF: 0.102 AC: 1556 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.152 AC: 529 AN: 3470

East Asian (EAS) AF: 0.00620 AC: 32 AN: 5162

South Asian (SAS) AF: 0.0675 AC: 326 AN: 4830

European-Finnish (FIN) AF: 0.118 AC: 1254 AN: 10600

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.116 AC: 7857 AN: 67974

Other (OTH) AF: 0.138 AC: 291 AN: 2110

Alfa AF: 0.115 Hom.: 3154

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

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	T
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	N
LIST_S2	Benign	0.055	.;T;T
MetaRNN	Benign	0.0013	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.060	N;N;N
PhyloP100		-1.5
PrimateAI	Benign	0.21	T
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	T
GERP RS		-9.3
Varity_R		0.020
gMVP		0.36
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

Other links and lift over

dbSNP: rs1143679; hg19: chr16-31276811; COSMIC: COSV54938377;