rs7499077

Positions:

• chr16-31306184-G-A

Variant summary

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

The NM_000632.4(ITGAM):​c.1707+8230G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 151,942 control chromosomes in the GnomAD database, including 16,341 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 0.40 (16341 hom., cov: 31)
• Consequence: ITGAM NM_000632.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.614

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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.766 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITGAM	NM_000632.4	c.1707+8230G>A		intron_variant		ENST00000544665.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGAM	ENST00000544665.9	c.1707+8230G>A		intron_variant		1	NM_000632.4	P4
ITGAM	ENST00000567031.1	c.453+8530G>A		intron_variant		1
ITGAM	ENST00000648685.1	c.1710+8230G>A		intron_variant				A1

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60575 AN: 151822 Hom.: 16297 Cov.: 31

Gnomad AFR AF: 0.772

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.0162

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.254

Gnomad MID AF: 0.341

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.352

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

GnomAD4 genome AF: 0.399 AC: 60669 AN: 151942 Hom.: 16341 Cov.: 31 AF XY: 0.393 AC XY: 29178 AN XY: 74274

Gnomad4 AFR AF: 0.773

Gnomad4 AMR AF: 0.257

Gnomad4 ASJ AF: 0.243

Gnomad4 EAS AF: 0.0158

Gnomad4 SAS AF: 0.244

Gnomad4 FIN AF: 0.254

Gnomad4 NFE AF: 0.278

Gnomad4 OTH AF: 0.349

Alfa AF: 0.334 Hom.: 2328

Bravo AF: 0.410

Asia WGS AF: 0.196 AC: 681 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.90
DANN	Benign	0.19

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: rs7499077; hg19: chr16-31317505; COSMIC: COSV54941684;