16-31268215-T-C

Variant names:

• chr16-31268215-T-C
• rs8048583
• NM_000632.4:c.427+2068T>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.427+2068T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.679 in 152,016 control chromosomes in the GnomAD database, including 35,354 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 0.68 (35354 hom., cov: 31)
• Consequence: ITGAM NM_000632.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0710
• Publications: 20 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.742 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGAM	NM_000632.4	c.427+2068T>C		intron_variant	Intron 5 of 29	ENST00000544665.9	NP_000623.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGAM	ENST00000544665.9	c.427+2068T>C		intron_variant	Intron 5 of 29	1	NM_000632.4	ENSP00000441691.3
ITGAM	ENST00000648685.1	c.427+2068T>C		intron_variant	Intron 5 of 29			ENSP00000496959.1

Frequencies

GnomAD3 genomes AF: 0.679 AC: 103083 AN: 151898 Hom.: 35321 Cov.: 31

Gnomad AFR AF: 0.749

Gnomad AMI AF: 0.623

Gnomad AMR AF: 0.593

Gnomad ASJ AF: 0.803

Gnomad EAS AF: 0.707

Gnomad SAS AF: 0.464

Gnomad FIN AF: 0.595

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.674

Gnomad OTH AF: 0.711

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

GnomAD4 genome AF: 0.679 AC: 103161 AN: 152016 Hom.: 35354 Cov.: 31 AF XY: 0.672 AC XY: 49945 AN XY: 74312

African (AFR) AF: 0.749 AC: 31056 AN: 41460

American (AMR) AF: 0.592 AC: 9040 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.803 AC: 2785 AN: 3470

East Asian (EAS) AF: 0.708 AC: 3653 AN: 5160

South Asian (SAS) AF: 0.465 AC: 2241 AN: 4822

European-Finnish (FIN) AF: 0.595 AC: 6279 AN: 10552

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

European-Non Finnish (NFE) AF: 0.674 AC: 45793 AN: 67978

Other (OTH) AF: 0.709 AC: 1495 AN: 2108

Alfa AF: 0.680 Hom.: 59244

Bravo AF: 0.686

Asia WGS AF: 0.581 AC: 2019 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.7
DANN	Benign	0.56
PhyloP100		0.071
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: rs8048583; hg19: chr16-31279536;