rs9937837

chr16-31287618-T-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.97).
• 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/exons	MANE	UniProt
ITGAM	NM_000632.4	c.1356+9509T>G		intron_variant		ENST00000544665.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGAM	ENST00000544665.9	c.1356+9509T>G		intron_variant		1	NM_000632.4	P4
ITGAM	ENST00000567031.1	c.313-9896T>G		intron_variant		1
ITGAM	ENST00000648685.1	c.1356+9509T>G		intron_variant				A1

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

Gnomad4 AFR AF: 0.729

Gnomad4 AMR AF: 0.253

Gnomad4 ASJ AF: 0.242

Gnomad4 EAS AF: 0.0156

Gnomad4 SAS AF: 0.243

Gnomad4 FIN AF: 0.252

Gnomad4 NFE AF: 0.277

Gnomad4 OTH AF: 0.340

Alfa AF: 0.283 Hom.: 13516

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

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: rs9937837; hg19: chr16-31298939;