rs11865830

Variant names:

• chr16-31260224-G-A
• rs11865830
• NM_000632.4:c.28+132G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 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=-0.91).
• 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 rank	MANE	Protein	UniProt
ITGAM	NM_000632.4	c.28+132G>A		intron_variant	Intron 1 of 29	ENST00000544665.9	NP_000623.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGAM	ENST00000544665.9	c.28+132G>A		intron_variant	Intron 1 of 29	1	NM_000632.4	ENSP00000441691.3
ITGAM	ENST00000648685.1	c.28+132G>A		intron_variant	Intron 1 of 29			ENSP00000496959.1

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

African (AFR) AF: 0.669 AC: 9237 AN: 13806

American (AMR) AF: 0.640 AC: 12116 AN: 18938

Ashkenazi Jewish (ASJ) AF: 0.799 AC: 11306 AN: 14146

East Asian (EAS) AF: 0.780 AC: 24628 AN: 31588

South Asian (SAS) AF: 0.472 AC: 22684 AN: 48094

European-Finnish (FIN) AF: 0.624 AC: 18948 AN: 30376

Middle Eastern (MID) AF: 0.799 AC: 1758 AN: 2200

European-Non Finnish (NFE) AF: 0.695 AC: 238280 AN: 342934

Other (OTH) AF: 0.694 AC: 19992 AN: 28826

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

African (AFR) AF: 0.665 AC: 27540 AN: 41404

American (AMR) AF: 0.649 AC: 9908 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.812 AC: 2819 AN: 3470

East Asian (EAS) AF: 0.717 AC: 3690 AN: 5148

South Asian (SAS) AF: 0.460 AC: 2220 AN: 4824

European-Finnish (FIN) AF: 0.629 AC: 6649 AN: 10566

Middle Eastern (MID) AF: 0.867 AC: 255 AN: 294

European-Non Finnish (NFE) AF: 0.693 AC: 47089 AN: 67962

Other (OTH) AF: 0.708 AC: 1492 AN: 2106

Alfa AF: 0.673 Hom.: 7029

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
PhyloP100		0.058
PromoterAI		-0.0056	Neutral
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: rs11865830; hg19: chr16-31271545;