16-31275827-A-T

Variant names:

• chr16-31275827-A-T
• rs9936831
• NM_000632.4:c.1009+128A>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.1009+128A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 809,402 control chromosomes in the GnomAD database, including 9,396 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 0.18 (3367 hom., cov: 31)
  • Exomes 𝑓: 0.12 (6029 hom.)
• 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: 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 = 0.331 is higher than 0.05.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.184 AC: 27940 AN: 151790 Hom.: 3352 Cov.: 31

Gnomad AFR AF: 0.335

Gnomad AMI AF: 0.191

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.00656

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.185

GnomAD4 exome AF: 0.123 AC: 81108 AN: 657492 Hom.: 6029 AF XY: 0.125 AC XY: 42109 AN XY: 336708

African (AFR) AF: 0.334 AC: 5311 AN: 15878

American (AMR) AF: 0.108 AC: 2053 AN: 19084

Ashkenazi Jewish (ASJ) AF: 0.160 AC: 2382 AN: 14862

East Asian (EAS) AF: 0.00136 AC: 42 AN: 30992

South Asian (SAS) AF: 0.191 AC: 9341 AN: 48902

European-Finnish (FIN) AF: 0.117 AC: 4148 AN: 35594

Middle Eastern (MID) AF: 0.167 AC: 389 AN: 2324

European-Non Finnish (NFE) AF: 0.116 AC: 52974 AN: 457242

Other (OTH) AF: 0.137 AC: 4468 AN: 32614

GnomAD4 genome AF: 0.184 AC: 28000 AN: 151910 Hom.: 3367 Cov.: 31 AF XY: 0.184 AC XY: 13638 AN XY: 74274

African (AFR) AF: 0.336 AC: 13909 AN: 41400

American (AMR) AF: 0.136 AC: 2069 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.175 AC: 607 AN: 3468

East Asian (EAS) AF: 0.00638 AC: 33 AN: 5170

South Asian (SAS) AF: 0.203 AC: 976 AN: 4810

European-Finnish (FIN) AF: 0.122 AC: 1292 AN: 10548

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.125 AC: 8500 AN: 67966

Other (OTH) AF: 0.184 AC: 385 AN: 2096

Alfa AF: 0.148 Hom.: 258

Bravo AF: 0.188

Asia WGS AF: 0.118 AC: 413 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	2.1
DANN	Benign	0.34
PhyloP100		-0.33
PromoterAI		0.0031	Neutral
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: rs9936831; hg19: chr16-31287148;