rs7193943

Variant names:

• chr16-31259742-G-A
• rs7193943
• NM_000632.4:c.-323G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-31259742-G-A
• chr16-31259742-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000632.4(ITGAM):​c.-323G>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.692 in 151,984 control chromosomes in the GnomAD database, including 36,603 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 0.69 (36603 hom., cov: 31)
• Consequence: ITGAM NM_000632.4 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38
• Publications: 17 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.728 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGAM	NM_000632.4	c.-323G>A		upstream_gene_variant		ENST00000544665.9	NP_000623.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGAM	ENST00000544665.9	c.-323G>A		upstream_gene_variant		1	NM_000632.4	ENSP00000441691.3
ITGAM	ENST00000648685.1	c.-323G>A		upstream_gene_variant				ENSP00000496959.1

Frequencies

GnomAD3 genomes AF: 0.692 AC: 105115 AN: 151866 Hom.: 36577 Cov.: 31

Gnomad AFR AF: 0.735

Gnomad AMI AF: 0.626

Gnomad AMR AF: 0.656

Gnomad ASJ AF: 0.784

Gnomad EAS AF: 0.716

Gnomad SAS AF: 0.461

Gnomad FIN AF: 0.630

Gnomad MID AF: 0.858

Gnomad NFE AF: 0.693

Gnomad OTH AF: 0.733

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

GnomAD4 genome AF: 0.692 AC: 105185 AN: 151984 Hom.: 36603 Cov.: 31 AF XY: 0.686 AC XY: 50951 AN XY: 74264

African (AFR) AF: 0.735 AC: 30457 AN: 41460

American (AMR) AF: 0.656 AC: 9993 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.784 AC: 2718 AN: 3468

East Asian (EAS) AF: 0.717 AC: 3688 AN: 5146

South Asian (SAS) AF: 0.461 AC: 2220 AN: 4812

European-Finnish (FIN) AF: 0.630 AC: 6651 AN: 10564

Middle Eastern (MID) AF: 0.854 AC: 251 AN: 294

European-Non Finnish (NFE) AF: 0.693 AC: 47098 AN: 67980

Other (OTH) AF: 0.730 AC: 1539 AN: 2108

Alfa AF: 0.701 Hom.: 57087

Bravo AF: 0.703

Asia WGS AF: 0.585 AC: 2033 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.21
DANN	Benign	0.69
PhyloP100		-1.4
PromoterAI		-0.045	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7193943; hg19: chr16-31271063;