rs11865830

Positions:

• chr16-31260224-G-A
• chr16-31260224-G-C
• chr16-31260224-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000632.4(ITGAM):​c.28+132G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.675 in 682,854 control chromosomes in the GnomAD database, including 158,330 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 0.67 (34643 hom., cov: 30)
  • Exomes 𝑓: 0.68 (123687 hom.)
• Consequence: ITGAM NM_000632.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0580

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.697 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITGAM	NM_000632.4	c.28+132G>A		intron_variant		ENST00000544665.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGAM	ENST00000544665.9	c.28+132G>A		intron_variant		1	NM_000632.4	P4
ITGAM	ENST00000648685.1	c.28+132G>A		intron_variant				A1

Frequencies

GnomAD3 genomes AF: 0.673 AC: 102163 AN: 151828 Hom.: 34625 Cov.: 30

Gnomad AFR AF: 0.665

Gnomad AMI AF: 0.624

Gnomad AMR AF: 0.649

Gnomad ASJ AF: 0.812

Gnomad EAS AF: 0.716

Gnomad SAS AF: 0.460

Gnomad FIN AF: 0.629

Gnomad MID AF: 0.870

Gnomad NFE AF: 0.693

Gnomad OTH AF: 0.711

GnomAD4 exome AF: 0.676 AC: 358949 AN: 530908 Hom.: 123687 AF XY: 0.669 AC XY: 186318 AN XY: 278444

Gnomad4 AFR exome AF: 0.669

Gnomad4 AMR exome AF: 0.640

Gnomad4 ASJ exome AF: 0.799

Gnomad4 EAS exome AF: 0.780

Gnomad4 SAS exome AF: 0.472

Gnomad4 FIN exome AF: 0.624

Gnomad4 NFE exome AF: 0.695

Gnomad4 OTH exome AF: 0.694

GnomAD4 genome AF: 0.673 AC: 102230 AN: 151946 Hom.: 34643 Cov.: 30 AF XY: 0.667 AC XY: 49549 AN XY: 74264

Gnomad4 AFR AF: 0.665

Gnomad4 AMR AF: 0.649

Gnomad4 ASJ AF: 0.812

Gnomad4 EAS AF: 0.717

Gnomad4 SAS AF: 0.460

Gnomad4 FIN AF: 0.629

Gnomad4 NFE AF: 0.693

Gnomad4 OTH AF: 0.708

Alfa AF: 0.672 Hom.: 5959

Bravo AF: 0.680

Asia WGS AF: 0.584 AC: 2032 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.0
DANN	Benign	0.47

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

LitVar

Other links and lift over

dbSNP: rs11865830; hg19: chr16-31271545;