rs9937837

Variant names:

• chr16-31287618-T-G
• rs9937837
• NM_000632.4:c.1356+9509T>G

Variant summary

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

The NM_000632.4(ITGAM):​c.1356+9509T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 151,958 control chromosomes in the GnomAD database, including 14,932 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 0.39 (14932 hom., cov: 31)
• Consequence: ITGAM NM_000632.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.570
• Publications: 36 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.722 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGAM	NM_000632.4	c.1356+9509T>G		intron_variant	Intron 12 of 29	ENST00000544665.9	NP_000623.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGAM	ENST00000544665.9	c.1356+9509T>G		intron_variant	Intron 12 of 29	1	NM_000632.4	ENSP00000441691.3
ITGAM	ENST00000567031.1	c.311-9896T>G		intron_variant	Intron 3 of 4	1		ENSP00000454568.1
ITGAM	ENST00000648685.1	c.1356+9509T>G		intron_variant	Intron 12 of 29			ENSP00000496959.1

Frequencies

GnomAD3 genomes AF: 0.386 AC: 58621 AN: 151840 Hom.: 14888 Cov.: 31

Gnomad AFR AF: 0.729

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.253

Gnomad ASJ AF: 0.242

Gnomad EAS AF: 0.0160

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.277

Gnomad OTH AF: 0.342

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

GnomAD4 genome AF: 0.386 AC: 58717 AN: 151958 Hom.: 14932 Cov.: 31 AF XY: 0.380 AC XY: 28219 AN XY: 74290

African (AFR) AF: 0.729 AC: 30190 AN: 41398

American (AMR) AF: 0.253 AC: 3855 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.242 AC: 839 AN: 3468

East Asian (EAS) AF: 0.0156 AC: 81 AN: 5178

South Asian (SAS) AF: 0.243 AC: 1175 AN: 4828

European-Finnish (FIN) AF: 0.252 AC: 2663 AN: 10568

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.277 AC: 18845 AN: 67940

Other (OTH) AF: 0.340 AC: 719 AN: 2112

Alfa AF: 0.301 Hom.: 35700

Bravo AF: 0.396

Asia WGS AF: 0.199 AC: 691 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.1
DANN	Benign	0.57
PhyloP100		-0.57
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: rs9937837; hg19: chr16-31298939;