chr16-31332448-T-C

Position:

• chr16-31332448-T-C

Variant summary

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

The ENST00000544665.9(ITGAM):​c.*741T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.727 in 152,214 control chromosomes in the GnomAD database, including 41,282 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 (41281 hom., cov: 33)
  • Exomes 𝑓: 0.50 (1 hom.)
• Consequence: ITGAM ENST00000544665.9 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0640

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.89 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGAM	NM_000632.4	c.*741T>C		3_prime_UTR_variant	30/30	ENST00000544665.9	NP_000623.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGAM	ENST00000544665.9	c.*741T>C		3_prime_UTR_variant	30/30	1	NM_000632.4	ENSP00000441691.3
ITGAM	ENST00000648685.1	c.*741T>C		3_prime_UTR_variant	30/30			ENSP00000496959.1

Frequencies

GnomAD3 genomes AF: 0.727 AC: 110554 AN: 152090 Hom.: 41247 Cov.: 33

Gnomad AFR AF: 0.898

Gnomad AMI AF: 0.624

Gnomad AMR AF: 0.607

Gnomad ASJ AF: 0.808

Gnomad EAS AF: 0.704

Gnomad SAS AF: 0.463

Gnomad FIN AF: 0.604

Gnomad MID AF: 0.861

Gnomad NFE AF: 0.685

Gnomad OTH AF: 0.737

GnomAD4 exome AF: 0.500 AC: 3 AN: 6 Hom.: 1 Cov.: 0 AF XY: 0.750 AC XY: 3 AN XY: 4

Gnomad4 FIN exome AF: 0.500

GnomAD4 genome AF: 0.727 AC: 110639 AN: 152208 Hom.: 41281 Cov.: 33 AF XY: 0.718 AC XY: 53457 AN XY: 74406

Gnomad4 AFR AF: 0.898

Gnomad4 AMR AF: 0.607

Gnomad4 ASJ AF: 0.808

Gnomad4 EAS AF: 0.705

Gnomad4 SAS AF: 0.463

Gnomad4 FIN AF: 0.604

Gnomad4 NFE AF: 0.685

Gnomad4 OTH AF: 0.735

Alfa AF: 0.707 Hom.: 36468

Bravo AF: 0.740

Asia WGS AF: 0.585 AC: 2034 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.5
DANN	Benign	0.60

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4597342; hg19: chr16-31343769;