16-31332448-T-C

Variant names:

• chr16-31332448-T-C
• rs4597342
• NM_000632.4:c.*741T>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.*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 NM_000632.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0640
• Publications: 28 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

ENSG00000289930 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGAM	NM_000632.4	MANE Select	c.*741T>C		3_prime_UTR	Exon 30 of 30	NP_000623.2
	ITGAM	NM_001145808.2		c.*741T>C		3_prime_UTR	Exon 30 of 30	NP_001139280.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGAM	ENST00000544665.9	TSL:1 MANE Select	c.*741T>C		3_prime_UTR	Exon 30 of 30	ENSP00000441691.3
	ITGAM	ENST00000648685.1		c.*741T>C		3_prime_UTR	Exon 30 of 30	ENSP00000496959.1
	ENSG00000289930	ENST00000777754.1		n.571-6740A>G		intron	N/A

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 3 AN: 6

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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

African (AFR) AF: 0.898 AC: 37308 AN: 41552

American (AMR) AF: 0.607 AC: 9274 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.808 AC: 2799 AN: 3466

East Asian (EAS) AF: 0.705 AC: 3653 AN: 5180

South Asian (SAS) AF: 0.463 AC: 2233 AN: 4822

European-Finnish (FIN) AF: 0.604 AC: 6393 AN: 10576

Middle Eastern (MID) AF: 0.861 AC: 253 AN: 294

European-Non Finnish (NFE) AF: 0.685 AC: 46605 AN: 68008

Other (OTH) AF: 0.735 AC: 1553 AN: 2114

Alfa AF: 0.711 Hom.: 48342

Bravo AF: 0.740

Asia WGS AF: 0.585 AC: 2034 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.5
DANN	Benign	0.60
PhyloP100		-0.064
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs4597342; hg19: chr16-31343769;