rs12928810

Positions:

• chr16-31300394-G-A

Variant summary

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

The ENST00000544665.9(ITGAM):​c.1707+2440G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 152,108 control chromosomes in the GnomAD database, including 3,065 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 0.18 (3065 hom., cov: 32)
• Consequence: ITGAM ENST00000544665.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGAM	NM_000632.4	c.1707+2440G>A		intron_variant		ENST00000544665.9	NP_000623.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGAM	ENST00000544665.9	c.1707+2440G>A		intron_variant		1	NM_000632.4	ENSP00000441691	P4
ITGAM	ENST00000567031.1	c.453+2740G>A		intron_variant		1		ENSP00000454568
ITGAM	ENST00000648685.1	c.1710+2440G>A		intron_variant				ENSP00000496959	A1

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27076 AN: 151990 Hom.: 3047 Cov.: 32

Gnomad AFR AF: 0.314

Gnomad AMI AF: 0.191

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.0143

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.176

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

GnomAD4 genome AF: 0.178 AC: 27139 AN: 152108 Hom.: 3065 Cov.: 32 AF XY: 0.177 AC XY: 13196 AN XY: 74354

Gnomad4 AFR AF: 0.314

Gnomad4 AMR AF: 0.133

Gnomad4 ASJ AF: 0.175

Gnomad4 EAS AF: 0.0139

Gnomad4 SAS AF: 0.202

Gnomad4 FIN AF: 0.122

Gnomad4 NFE AF: 0.125

Gnomad4 OTH AF: 0.175

Alfa AF: 0.140 Hom.: 1817

Bravo AF: 0.181

Asia WGS AF: 0.119 AC: 414 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.3
DANN	Benign	0.52

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: rs12928810; hg19: chr16-31311715; COSMIC: COSV54941674;