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rs1143679

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000632(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 0.108 in 152038 control chromosomes in the gnomAD Genomes database, including 974 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 ( 974 hom., cov: 31)
Exomes 𝑓: 0.097 ( 1170 hom. )

Consequence

ITGAM
NM_000632 missense

Scores

12

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.52

Links

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 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_single_submitter, 1 stars.
BA1
?
GnomAd 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
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
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:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeNov 03, 2022- -

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
0.027
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

Find out SpliceAI 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;