rs9936831

Variant names:

• chr16-31275827-A-C
• rs9936831
• NM_000632.4:c.1009+128A>C

Your query was ambiguous. Multiple possible variants found:

• chr16-31275827-A-C
• chr16-31275827-A-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000632.4(ITGAM):​c.1009+128A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ITGAM NM_000632.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.330
• Publications: 10 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGAM	NM_000632.4	c.1009+128A>C		intron_variant	Intron 9 of 29	ENST00000544665.9	NP_000623.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGAM	ENST00000544665.9	c.1009+128A>C		intron_variant	Intron 9 of 29	1	NM_000632.4	ENSP00000441691.3
ITGAM	ENST00000567031.1	c.106+128A>C		intron_variant	Intron 1 of 4	1		ENSP00000454568.1
ITGAM	ENST00000648685.1	c.1009+128A>C		intron_variant	Intron 9 of 29			ENSP00000496959.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 658316 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 337116

African (AFR) AF: 0.00 AC: 0 AN: 15926

American (AMR) AF: 0.00 AC: 0 AN: 19098

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14890

East Asian (EAS) AF: 0.00 AC: 0 AN: 30992

South Asian (SAS) AF: 0.00 AC: 0 AN: 48998

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2330

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 457808

Other (OTH) AF: 0.00 AC: 0 AN: 32646

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 258

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.3
DANN	Benign	0.20
PhyloP100		-0.33
PromoterAI		0.0045	Neutral

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: rs9936831; hg19: chr16-31287148;