rs9888739

Variant names:

• chr16-31301932-C-T
• rs9888739
• NM_000632.4:c.1707+3978C>T

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+3978C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 151,968 control chromosomes in the GnomAD database, including 7,873 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 0.25 (7873 hom., cov: 32)
• Consequence: ITGAM NM_000632.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.133
• Publications: 78 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.562 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGAM	NM_000632.4	c.1707+3978C>T		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+3978C>T		intron_variant	Intron 14 of 29	1	NM_000632.4	ENSP00000441691.3
ITGAM	ENST00000567031.1	c.451+4278C>T		intron_variant	Intron 4 of 4	1		ENSP00000454568.1
ITGAM	ENST00000648685.1	c.1710+3978C>T		intron_variant	Intron 14 of 29			ENSP00000496959.1

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38134 AN: 151850 Hom.: 7837 Cov.: 32

Gnomad AFR AF: 0.567

Gnomad AMI AF: 0.191

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.0143

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.233

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

GnomAD4 genome AF: 0.252 AC: 38223 AN: 151968 Hom.: 7873 Cov.: 32 AF XY: 0.248 AC XY: 18436 AN XY: 74262

African (AFR) AF: 0.568 AC: 23534 AN: 41438

American (AMR) AF: 0.160 AC: 2440 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.175 AC: 607 AN: 3464

East Asian (EAS) AF: 0.0139 AC: 72 AN: 5180

South Asian (SAS) AF: 0.203 AC: 975 AN: 4814

European-Finnish (FIN) AF: 0.123 AC: 1293 AN: 10528

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.126 AC: 8580 AN: 67962

Other (OTH) AF: 0.232 AC: 490 AN: 2108

Alfa AF: 0.160 Hom.: 12351

Bravo AF: 0.265

Asia WGS AF: 0.132 AC: 458 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.0
DANN	Benign	0.30
PhyloP100		-0.13
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: rs9888739; hg19: chr16-31313253;