rs9888879

Variant names:

• chr16-31299051-T-C
• rs9888879
• NM_000632.4:c.1707+1097T>C

Variant summary

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

The NM_000632.4(ITGAM):​c.1707+1097T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 152,066 control chromosomes in the GnomAD database, including 7,908 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 0.25 (7908 hom., cov: 31)
• Consequence: ITGAM NM_000632.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00100
• Publications: 15 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 (AFR) allele frequency at 95% confidence interval = 0.563 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGAM	NM_000632.4	c.1707+1097T>C		intron_variant	Intron 14 of 29	ENST00000544665.9	NP_000623.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGAM	ENST00000544665.9	c.1707+1097T>C		intron_variant	Intron 14 of 29	1	NM_000632.4	ENSP00000441691.3
ITGAM	ENST00000567031.1	c.451+1397T>C		intron_variant	Intron 4 of 4	1		ENSP00000454568.1
ITGAM	ENST00000648685.1	c.1710+1097T>C		intron_variant	Intron 14 of 29			ENSP00000496959.1

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38158 AN: 151946 Hom.: 7872 Cov.: 31

Gnomad AFR AF: 0.569

Gnomad AMI AF: 0.191

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.0141

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.233

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

GnomAD4 genome AF: 0.252 AC: 38247 AN: 152066 Hom.: 7908 Cov.: 31 AF XY: 0.248 AC XY: 18435 AN XY: 74356

African (AFR) AF: 0.569 AC: 23580 AN: 41408

American (AMR) AF: 0.159 AC: 2430 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.176 AC: 609 AN: 3470

East Asian (EAS) AF: 0.0137 AC: 71 AN: 5184

South Asian (SAS) AF: 0.201 AC: 970 AN: 4822

European-Finnish (FIN) AF: 0.122 AC: 1291 AN: 10602

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.126 AC: 8573 AN: 67996

Other (OTH) AF: 0.232 AC: 491 AN: 2114

Alfa AF: 0.166 Hom.: 12485

Bravo AF: 0.265

Asia WGS AF: 0.132 AC: 460 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	3.1
DANN	Benign	0.60
PhyloP100		0.0010
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: rs9888879; hg19: chr16-31310372;