rs7193268

Positions:

• chr16-31329676-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000544665.9(ITGAM):​c.2869-122C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 736,286 control chromosomes in the GnomAD database, including 12,085 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 0.19 (3306 hom., cov: 31)
  • Exomes 𝑓: 0.16 (8779 hom.)
• Consequence: ITGAM ENST00000544665.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.446

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGAM	NM_000632.4	c.2869-122C>T		intron_variant		ENST00000544665.9	NP_000623.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGAM	ENST00000544665.9	c.2869-122C>T		intron_variant		1	NM_000632.4	ENSP00000441691	P4
ITGAM	ENST00000648685.1	c.2872-122C>T		intron_variant				ENSP00000496959	A1
ITGAM	ENST00000567178.1	n.271-122C>T		intron_variant, non_coding_transcript_variant		5
ITGAM	ENST00000569746.1	n.303-122C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29486 AN: 151884 Hom.: 3295 Cov.: 31

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.0144

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.201

GnomAD4 exome AF: 0.161 AC: 93964 AN: 584284 Hom.: 8779 AF XY: 0.165 AC XY: 50552 AN XY: 306714

Gnomad4 AFR exome AF: 0.291

Gnomad4 AMR exome AF: 0.125

Gnomad4 ASJ exome AF: 0.244

Gnomad4 EAS exome AF: 0.00369

Gnomad4 SAS exome AF: 0.249

Gnomad4 FIN exome AF: 0.128

Gnomad4 NFE exome AF: 0.157

Gnomad4 OTH exome AF: 0.174

GnomAD4 genome AF: 0.194 AC: 29538 AN: 152002 Hom.: 3306 Cov.: 31 AF XY: 0.193 AC XY: 14325 AN XY: 74292

Gnomad4 AFR AF: 0.290

Gnomad4 AMR AF: 0.158

Gnomad4 ASJ AF: 0.250

Gnomad4 EAS AF: 0.0140

Gnomad4 SAS AF: 0.250

Gnomad4 FIN AF: 0.131

Gnomad4 NFE AF: 0.160

Gnomad4 OTH AF: 0.202

Alfa AF: 0.177 Hom.: 1623

Bravo AF: 0.197

Asia WGS AF: 0.143 AC: 499 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.3
DANN	Benign	0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7193268; hg19: chr16-31340997;