NM_000632.4:c.8T>G

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_000632.4(ITGAM):c.8T>G(p.Leu3Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000935 in 1,325,782 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L3F) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000022 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00010 ( 0 hom. )

Consequence

ITGAM
NM_000632.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.924

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

systemic lupus erythematosus
Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

ITGAM links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06516495).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000632.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGAM	NM_000632.4	MANE Select	c.8T>G	p.Leu3Arg	missense	Exon 1 of 30	NP_000623.2	P11215-1
	ITGAM	NM_001145808.2		c.8T>G	p.Leu3Arg	missense	Exon 1 of 30	NP_001139280.1	P11215-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ITGAM	ENST00000544665.9	TSL:1 MANE Select	c.8T>G	p.Leu3Arg	missense	Exon 1 of 30	ENSP00000441691.3	P11215-1
ITGAM	ENST00000943361.1		c.8T>G	p.Leu3Arg	missense	Exon 1 of 30	ENSP00000613420.1
ITGAM	ENST00000648685.1		c.8T>G	p.Leu3Arg	missense	Exon 1 of 30	ENSP00000496959.1	P11215-2

Frequencies

GnomAD3 genomes

AF:

0.0000216

AC:

AN:

138792

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000263

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000727

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000156

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000291

AC:

AN:

205872

AF XY:

0.00000908

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000134

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000220

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000102

AC:

121

AN:

1186990

Hom.:

Cov.:

AF XY:

0.0000989

AC XY:

AN XY:

586204

show subpopulations

African (AFR)

AF:

0.000115

AC:

AN:

26140

American (AMR)

AF:

0.000119

AC:

AN:

33694

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16698

East Asian (EAS)

AF:

0.00

AC:

AN:

17260

South Asian (SAS)

AF:

0.00

AC:

AN:

79216

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31408

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4472

European-Non Finnish (NFE)

AF:

0.000114

AC:

107

AN:

934520

Other (OTH)

AF:

0.000161

AC:

AN:

43582

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.443

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000216

AC:

AN:

138792

Hom.:

Cov.:

AF XY:

0.0000149

AC XY:

AN XY:

66950

show subpopulations

African (AFR)

AF:

0.0000263

AC:

AN:

38072

American (AMR)

AF:

0.0000727

AC:

AN:

13756

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3312

East Asian (EAS)

AF:

0.00

AC:

AN:

3996

South Asian (SAS)

AF:

0.00

AC:

AN:

3876

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8360

Middle Eastern (MID)

AF:

0.00

AC:

AN:

304

European-Non Finnish (NFE)

AF:

0.0000156

AC:

AN:

64288

Other (OTH)

AF:

0.00

AC:

AN:

1964

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000712

Hom.:

ExAC

AF:

0.0000250

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.047

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.45

CADD

Benign

3.4

(source)

DANN

Benign

0.82

DEOGEN2

Benign

0.049

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.021

LIST_S2

Benign

0.32

M_CAP

Benign

0.017

MetaRNN

Benign

0.065

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

PhyloP100

-0.92

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.77

REVEL

Benign

0.095

Sift

Benign

0.24

Sift4G

Benign

0.34

Polyphen

0.0

Vest4

0.28

MutPred

0.65

Loss of stability (P = 0.0129)

MVP

0.29

MPC

0.42

ClinPred

0.036

GERP RS

-4.7

PromoterAI

0.070

Neutral

(source)

Varity_R

0.11

gMVP

0.63

Mutation Taster

=91/9

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over