rs11150610

Variant names:

• chr16-31322915-C-A
• rs11150610
• NM_000632.4:c.2002+1288C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000632.4(ITGAM):​c.2002+1288C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 151,730 control chromosomes in the GnomAD database, including 9,699 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 0.33 (9699 hom., cov: 31)
• Consequence: ITGAM NM_000632.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.06
• Publications: 42 publications found

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGAM	NM_000632.4	c.2002+1288C>A		intron_variant	Intron 16 of 29	ENST00000544665.9	NP_000623.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGAM	ENST00000544665.9	c.2002+1288C>A		intron_variant	Intron 16 of 29	1	NM_000632.4	ENSP00000441691.3
ITGAM	ENST00000567031.1	c.452-1484C>A		intron_variant	Intron 4 of 4	1		ENSP00000454568.1
ITGAM	ENST00000648685.1	c.2005+1288C>A		intron_variant	Intron 16 of 29			ENSP00000496959.1

Frequencies

GnomAD3 genomes AF: 0.329 AC: 49914 AN: 151612 Hom.: 9699 Cov.: 31

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.565

Gnomad EAS AF: 0.688

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.402

Gnomad OTH AF: 0.382

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.329 AC: 49910 AN: 151730 Hom.: 9699 Cov.: 31 AF XY: 0.327 AC XY: 24217 AN XY: 74136

African (AFR) AF: 0.139 AC: 5767 AN: 41356

American (AMR) AF: 0.350 AC: 5330 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.565 AC: 1961 AN: 3468

East Asian (EAS) AF: 0.689 AC: 3544 AN: 5142

South Asian (SAS) AF: 0.216 AC: 1038 AN: 4800

European-Finnish (FIN) AF: 0.349 AC: 3667 AN: 10498

Middle Eastern (MID) AF: 0.524 AC: 153 AN: 292

European-Non Finnish (NFE) AF: 0.402 AC: 27333 AN: 67930

Other (OTH) AF: 0.381 AC: 799 AN: 2098

Alfa AF: 0.395 Hom.: 45700

Bravo AF: 0.332

Asia WGS AF: 0.385 AC: 1339 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.2
DANN	Benign	0.64
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11150610; hg19: chr16-31334236;