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rs1143679

Variant summary

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

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. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin 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
NM_000632.4 missense

Scores

12

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

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]

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/exons MANE UniProt
ITGAMNM_000632.4 linkuse as main transcriptc.230G>A p.Arg77His missense_variant 3/30 ENST00000544665.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ITGAMENST00000544665.9 linkuse as main transcriptc.230G>A p.Arg77His missense_variant 3/301 NM_000632.4 P4P11215-1
ITGAMENST00000648685.1 linkuse as main transcriptc.230G>A p.Arg77His missense_variant 3/30 A1P11215-2

Frequencies

GnomAD3 genomes
AF:
0.108
AC:
16424
AN:
152038
Hom.:
974
Cov.:
31
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.:
29
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.:
31
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:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJan 31, 2024- -
ITGAM-related condition Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesNov 12, 2019This 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
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.5
FATHMM_MKL
Benign
0.022
N
MetaRNN
Benign
0.0013
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.060
N;N;N
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.21
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

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.

Other links and lift over

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