16-31315385-C-T

Variant names:

• chr16-31315385-C-T
• rs11860650
• NM_000632.4:c.1708-5856C>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.1708-5856C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 152,096 control chromosomes in the GnomAD database, including 1,714 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 0.14 (1714 hom., cov: 31)
• Consequence: ITGAM NM_000632.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.99
• Publications: 28 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 (SAS) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGAM	NM_000632.4	c.1708-5856C>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.1708-5856C>T		intron_variant	Intron 14 of 29	1	NM_000632.4	ENSP00000441691.3
ITGAM	ENST00000567031.1	c.452-9014C>T		intron_variant	Intron 4 of 4	1		ENSP00000454568.1
ITGAM	ENST00000648685.1	c.1711-5856C>T		intron_variant	Intron 14 of 29			ENSP00000496959.1

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21619 AN: 151978 Hom.: 1713 Cov.: 31

Gnomad AFR AF: 0.189

Gnomad AMI AF: 0.191

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.0142

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.158

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

GnomAD4 genome AF: 0.142 AC: 21632 AN: 152096 Hom.: 1714 Cov.: 31 AF XY: 0.143 AC XY: 10603 AN XY: 74366

African (AFR) AF: 0.189 AC: 7823 AN: 41480

American (AMR) AF: 0.119 AC: 1818 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 603 AN: 3470

East Asian (EAS) AF: 0.0139 AC: 72 AN: 5184

South Asian (SAS) AF: 0.201 AC: 970 AN: 4814

European-Finnish (FIN) AF: 0.122 AC: 1287 AN: 10560

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.125 AC: 8499 AN: 67978

Other (OTH) AF: 0.158 AC: 333 AN: 2114

Alfa AF: 0.129 Hom.: 2267

Bravo AF: 0.141

Asia WGS AF: 0.108 AC: 376 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.89
DANN	Benign	0.57
PhyloP100		-2.0
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: rs11860650; hg19: chr16-31326706;