chr16-31325198-T-C

Variant names:

• chr16-31325198-T-C
• rs7206295
• NM_000632.4:c.2364-65T>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.2364-65T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.681 in 1,550,862 control chromosomes in the GnomAD database, including 364,741 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 0.73 (41196 hom., cov: 31)
  • Exomes 𝑓: 0.68 (323545 hom.)
• Consequence: ITGAM NM_000632.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11
• Publications: 22 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.888 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGAM	NM_000632.4	c.2364-65T>C		intron_variant	Intron 19 of 29	ENST00000544665.9	NP_000623.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGAM	ENST00000544665.9	c.2364-65T>C		intron_variant	Intron 19 of 29	1	NM_000632.4	ENSP00000441691.3
ITGAM	ENST00000648685.1	c.2367-65T>C		intron_variant	Intron 19 of 29			ENSP00000496959.1
ITGAM	ENST00000561838.1	n.180-65T>C		intron_variant	Intron 2 of 4	4

Frequencies

GnomAD3 genomes AF: 0.727 AC: 110398 AN: 151926 Hom.: 41159 Cov.: 31

Gnomad AFR AF: 0.895

Gnomad AMI AF: 0.624

Gnomad AMR AF: 0.609

Gnomad ASJ AF: 0.809

Gnomad EAS AF: 0.709

Gnomad SAS AF: 0.461

Gnomad FIN AF: 0.605

Gnomad MID AF: 0.864

Gnomad NFE AF: 0.686

Gnomad OTH AF: 0.739

GnomAD4 exome AF: 0.676 AC: 945193 AN: 1398818 Hom.: 323545 Cov.: 30 AF XY: 0.671 AC XY: 463801 AN XY: 691262

African (AFR) AF: 0.908 AC: 28988 AN: 31912

American (AMR) AF: 0.550 AC: 18896 AN: 34378

Ashkenazi Jewish (ASJ) AF: 0.796 AC: 17530 AN: 22024

East Asian (EAS) AF: 0.765 AC: 29793 AN: 38960

South Asian (SAS) AF: 0.472 AC: 36094 AN: 76446

European-Finnish (FIN) AF: 0.604 AC: 30245 AN: 50078

Middle Eastern (MID) AF: 0.805 AC: 4009 AN: 4980

European-Non Finnish (NFE) AF: 0.683 AC: 739597 AN: 1082256

Other (OTH) AF: 0.693 AC: 40041 AN: 57784

GnomAD4 genome AF: 0.727 AC: 110492 AN: 152044 Hom.: 41196 Cov.: 31 AF XY: 0.718 AC XY: 53366 AN XY: 74330

African (AFR) AF: 0.895 AC: 37150 AN: 41494

American (AMR) AF: 0.609 AC: 9285 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.809 AC: 2806 AN: 3470

East Asian (EAS) AF: 0.710 AC: 3651 AN: 5144

South Asian (SAS) AF: 0.461 AC: 2219 AN: 4816

European-Finnish (FIN) AF: 0.605 AC: 6402 AN: 10584

Middle Eastern (MID) AF: 0.864 AC: 254 AN: 294

European-Non Finnish (NFE) AF: 0.686 AC: 46601 AN: 67964

Other (OTH) AF: 0.737 AC: 1555 AN: 2110

Alfa AF: 0.708 Hom.: 49493

Bravo AF: 0.740

Asia WGS AF: 0.587 AC: 2041 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.6
DANN	Benign	0.29
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs7206295; hg19: chr16-31336519; COSMIC: COSV54943617; COSMIC: COSV54943617;