Genetic Variant ITGAM:c.2869-122C>T (chr16-31329676-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000632.4(ITGAM):c.2869-122C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 736,286 control chromosomes in the GnomAD database, including 12,085 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.19 ( 3306 hom., cov: 31)

Exomes 𝑓: 0.16 ( 8779 hom. )

Consequence

ITGAM
NM_000632.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.446

Publications

16 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGAM	NM_000632.4 link	c.2869-122C>T		intron_variant	Intron 24 of 29	ENST00000544665.9	NP_000623.2	P11215-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGAM	ENST00000544665.9 link	c.2869-122C>T		intron_variant	Intron 24 of 29	1	NM_000632.4	ENSP00000441691.3		P11215-1

Frequencies

GnomAD3 genomes

AF:

0.194

AC:

29486

AN:

151884

Hom.:

3295

Cov.:

show subpopulations

Gnomad AFR

AF:

0.290

Gnomad AMI

AF:

0.193

Gnomad AMR

AF:

0.158

Gnomad ASJ

AF:

0.250

Gnomad EAS

AF:

0.0144

Gnomad SAS

AF:

0.250

Gnomad FIN

AF:

0.131

Gnomad MID

AF:

0.256

Gnomad NFE

AF:

0.160

Gnomad OTH

AF:

0.201

GnomAD4 exome

AF:

0.161

AC:

93964

AN:

584284

Hom.:

8779

AF XY:

0.165

AC XY:

50552

AN XY:

306714

show subpopulations

African (AFR)

AF:

0.291

AC:

4422

AN:

15170

American (AMR)

AF:

0.125

AC:

2942

AN:

23452

Ashkenazi Jewish (ASJ)

AF:

0.244

AC:

3704

AN:

15180

East Asian (EAS)

AF:

0.00369

AC:

118

AN:

31976

South Asian (SAS)

AF:

0.249

AC:

13153

AN:

52910

European-Finnish (FIN)

AF:

0.128

AC:

5476

AN:

42900

Middle Eastern (MID)

AF:

0.254

AC:

581

AN:

2288

European-Non Finnish (NFE)

AF:

0.157

AC:

58286

AN:

370088

Other (OTH)

AF:

0.174

AC:

5282

AN:

30320

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

3946

7891

11837

15782

19728

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

860

1720

2580

3440

4300

<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:

0.194

AC:

29538

AN:

152002

Hom.:

3306

Cov.:

AF XY:

0.193

AC XY:

14325

AN XY:

74292

show subpopulations

African (AFR)

AF:

0.290

AC:

12023

AN:

41428

American (AMR)

AF:

0.158

AC:

2410

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.250

AC:

869

AN:

3470

East Asian (EAS)

AF:

0.0140

AC:

AN:

5140

South Asian (SAS)

AF:

0.250

AC:

1206

AN:

4820

European-Finnish (FIN)

AF:

0.131

AC:

1388

AN:

10586

Middle Eastern (MID)

AF:

0.262

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.160

AC:

10892

AN:

67952

Other (OTH)

AF:

0.202

AC:

426

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1178

2356

3533

4711

5889

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

308

616

924

1232

1540

<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:

0.178

Hom.:

2242

Bravo

AF:

0.197

Asia WGS

AF:

0.143

AC:

499

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

4.3

(source)

DANN

Benign

0.42

PhyloP100

-0.45

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over