rs6565227

Variant names:

• chr16-31317670-A-T
• rs6565227
• NM_000632.4:c.1708-3571A>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.1708-3571A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 152,078 control chromosomes in the GnomAD database, including 7,879 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 (7879 hom., cov: 32)
• Consequence: ITGAM NM_000632.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.04
• Publications: 6 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.562 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000632.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGAM	NM_000632.4	MANE Select	c.1708-3571A>T		intron	N/A	NP_000623.2
	ITGAM	NM_001145808.2		c.1711-3571A>T		intron	N/A	NP_001139280.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGAM	ENST00000544665.9	TSL:1 MANE Select	c.1708-3571A>T		intron	N/A	ENSP00000441691.3
	ITGAM	ENST00000567031.1	TSL:1	c.452-6729A>T		intron	N/A	ENSP00000454568.1
	ITGAM	ENST00000943361.1		c.1708-3571A>T		intron	N/A	ENSP00000613420.1

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38142 AN: 151958 Hom.: 7842 Cov.: 32

Gnomad AFR AF: 0.567

Gnomad AMI AF: 0.191

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.0143

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.231

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

GnomAD4 genome AF: 0.251 AC: 38232 AN: 152078 Hom.: 7879 Cov.: 32 AF XY: 0.248 AC XY: 18431 AN XY: 74322

African (AFR) AF: 0.568 AC: 23551 AN: 41460

American (AMR) AF: 0.160 AC: 2436 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.176 AC: 609 AN: 3470

East Asian (EAS) AF: 0.0139 AC: 72 AN: 5182

South Asian (SAS) AF: 0.201 AC: 966 AN: 4812

European-Finnish (FIN) AF: 0.123 AC: 1297 AN: 10568

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

European-Non Finnish (NFE) AF: 0.126 AC: 8585 AN: 68006

Other (OTH) AF: 0.230 AC: 484 AN: 2104

Alfa AF: 0.197 Hom.: 615

Bravo AF: 0.265

Asia WGS AF: 0.132 AC: 459 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.6
DANN	Benign	0.34
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: rs6565227; hg19: chr16-31328991;