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

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.52

Links

ITGAM (HGNC:6149):

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
ITGAM	NM_000632.4 linkuse as main transcript	c.230G>A	p.Arg77His	missense_variant	3/30	ENST00000544665.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGAM	ENST00000544665.9 linkuse as main transcript	c.230G>A	p.Arg77His	missense_variant	3/30	1	NM_000632.4	P4	P11215-1
ITGAM	ENST00000648685.1 linkuse as main transcript	c.230G>A	p.Arg77His	missense_variant	3/30			A1	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

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 submitter

clinical testing

Invitae

Nov 03, 2022

- -

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

0.027

Dann

Benign

0.90

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.022

MetaRNN

Benign

0.0013

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.060

N;N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.21

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Links

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over