chr16-31300394-G-A

Variant names:

• chr16-31300394-G-A
• rs12928810
• NM_000632.4:c.1707+2440G>A

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+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 NM_000632.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08
• Publications: 8 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=-0.98).
• 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 rank	MANE	Protein	UniProt
ITGAM	NM_000632.4	c.1707+2440G>A		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+2440G>A		intron_variant	Intron 14 of 29	1	NM_000632.4	ENSP00000441691.3
ITGAM	ENST00000567031.1	c.451+2740G>A		intron_variant	Intron 4 of 4	1		ENSP00000454568.1
ITGAM	ENST00000648685.1	c.1710+2440G>A		intron_variant	Intron 14 of 29			ENSP00000496959.1

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

African (AFR) AF: 0.314 AC: 13037 AN: 41478

American (AMR) AF: 0.133 AC: 2033 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.175 AC: 606 AN: 3468

East Asian (EAS) AF: 0.0139 AC: 72 AN: 5170

South Asian (SAS) AF: 0.202 AC: 973 AN: 4822

European-Finnish (FIN) AF: 0.122 AC: 1291 AN: 10570

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.125 AC: 8527 AN: 67994

Other (OTH) AF: 0.175 AC: 370 AN: 2112

Alfa AF: 0.141 Hom.: 5339

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
PhyloP100		-1.1
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: rs12928810; hg19: chr16-31311715; COSMIC: COSV54941674;