NM_000632.4:c.1707+8230G>A

Variant names:

• chr16-31306184-G-A
• rs7499077
• NM_000632.4:c.1707+8230G>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+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
• Publications: 6 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=-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 rank	MANE	Protein	UniProt
ITGAM	NM_000632.4	c.1707+8230G>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+8230G>A		intron_variant	Intron 14 of 29	1	NM_000632.4	ENSP00000441691.3
ITGAM	ENST00000567031.1	c.451+8530G>A		intron_variant	Intron 4 of 4	1		ENSP00000454568.1
ITGAM	ENST00000648685.1	c.1710+8230G>A		intron_variant	Intron 14 of 29			ENSP00000496959.1

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

African (AFR) AF: 0.773 AC: 32018 AN: 41440

American (AMR) AF: 0.257 AC: 3914 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.243 AC: 842 AN: 3466

East Asian (EAS) AF: 0.0158 AC: 82 AN: 5180

South Asian (SAS) AF: 0.244 AC: 1174 AN: 4816

European-Finnish (FIN) AF: 0.254 AC: 2678 AN: 10552

Middle Eastern (MID) AF: 0.332 AC: 97 AN: 292

European-Non Finnish (NFE) AF: 0.278 AC: 18878 AN: 67932

Other (OTH) AF: 0.349 AC: 736 AN: 2110

Alfa AF: 0.359 Hom.: 3103

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
PhyloP100		-0.61
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: rs7499077; hg19: chr16-31317505; COSMIC: COSV54941684;