rs1143678

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000632.4(ITGAM):c.3436C>T(p.Pro1146Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 1,606,686 control chromosomes in the GnomAD database, including 20,752 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 (★★).

Frequency

Genomes: 𝑓 0.17 ( 2395 hom., cov: 31)

Exomes 𝑓: 0.15 ( 18357 hom. )

Consequence

ITGAM
NM_000632.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.22

Publications

56 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:

ENSG00000289930 (HGNC:):

ENSG00000289930 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0047775805).

BP6

Variant 16-31331684-C-T is Benign according to our data. Variant chr16-31331684-C-T is described in ClinVar as Benign. ClinVar VariationId is 1164969.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.238 is higher than 0.05.

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.3436C>T	p.Pro1146Ser	missense	Exon 30 of 30	NP_000623.2	P11215-1
	ITGAM	NM_001145808.2		c.3439C>T	p.Pro1147Ser	missense	Exon 30 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.3436C>T	p.Pro1146Ser	missense	Exon 30 of 30	ENSP00000441691.3	P11215-1
ITGAM	ENST00000943361.1		c.3547C>T	p.Pro1183Ser	missense	Exon 30 of 30	ENSP00000613420.1
ITGAM	ENST00000648685.1		c.3439C>T	p.Pro1147Ser	missense	Exon 30 of 30	ENSP00000496959.1	P11215-2

Frequencies

GnomAD3 genomes

AF:

0.170

AC:

25799

AN:

151900

Hom.:

2394

Cov.:

show subpopulations

Gnomad AFR

AF:

0.208

Gnomad AMI

AF:

0.193

Gnomad AMR

AF:

0.149

Gnomad ASJ

AF:

0.223

Gnomad EAS

AF:

0.0147

Gnomad SAS

AF:

0.249

Gnomad FIN

AF:

0.128

Gnomad MID

AF:

0.247

Gnomad NFE

AF:

0.160

Gnomad OTH

AF:

0.187

GnomAD2 exomes

AF:

0.154

AC:

36271

AN:

234918

AF XY:

0.161

show subpopulations

Gnomad AFR exome

AF:

0.211

Gnomad AMR exome

AF:

0.103

Gnomad ASJ exome

AF:

0.210

Gnomad EAS exome

AF:

0.0114

Gnomad FIN exome

AF:

0.126

Gnomad NFE exome

AF:

0.160

Gnomad OTH exome

AF:

0.166

GnomAD4 exome

AF:

0.153

AC:

221942

AN:

1454664

Hom.:

18357

Cov.:

AF XY:

0.156

AC XY:

112964

AN XY:

722878

show subpopulations

African (AFR)

AF:

0.216

AC:

7202

AN:

33354

American (AMR)

AF:

0.109

AC:

4780

AN:

43850

Ashkenazi Jewish (ASJ)

AF:

0.214

AC:

5553

AN:

25908

East Asian (EAS)

AF:

0.00481

AC:

190

AN:

39488

South Asian (SAS)

AF:

0.250

AC:

21237

AN:

84956

European-Finnish (FIN)

AF:

0.126

AC:

6634

AN:

52756

Middle Eastern (MID)

AF:

0.252

AC:

1446

AN:

5748

European-Non Finnish (NFE)

AF:

0.149

AC:

164959

AN:

1108486

Other (OTH)

AF:

0.165

AC:

9941

AN:

60118

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

8488

16976

25464

33952

42440

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5826

11652

17478

23304

29130

<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:

0.170

AC:

25819

AN:

152022

Hom.:

2395

Cov.:

AF XY:

0.169

AC XY:

12588

AN XY:

74304

show subpopulations

African (AFR)

AF:

0.208

AC:

8638

AN:

41470

American (AMR)

AF:

0.149

AC:

2281

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.223

AC:

775

AN:

3470

East Asian (EAS)

AF:

0.0143

AC:

AN:

5158

South Asian (SAS)

AF:

0.250

AC:

1200

AN:

4808

European-Finnish (FIN)

AF:

0.128

AC:

1360

AN:

10590

Middle Eastern (MID)

AF:

0.252

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.160

AC:

10844

AN:

67938

Other (OTH)

AF:

0.188

AC:

397

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1048

2096

3144

4192

5240

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

282

564

846

1128

1410

<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:

0.170

Hom.:

4967

Bravo

AF:

0.170

TwinsUK

AF:

0.147

AC:

544

ALSPAC

AF:

0.141

AC:

543

ESP6500AA

AF:

0.194

AC:

755

ESP6500EA

AF:

0.153

AC:

1262

ExAC

AF:

0.155

AC:

18676

Asia WGS

AF:

0.137

AC:

475

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

ITGAM-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.10

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.51

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.54

MetaRNN

Benign

0.0048

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

PhyloP100

1.2

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.7

REVEL

Benign

0.087

Sift

Uncertain

0.018

Sift4G

Benign

0.087

Polyphen

0.72

Vest4

0.062

MPC

0.89

ClinPred

0.023

GERP RS

3.3

Varity_R

0.048

gMVP

0.23

Mutation Taster

=89/11

polymorphism (auto)

(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

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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