rs868875

chr19-7766280-A-G

Variant summary

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

The NM_014257.5(CLEC4M):c.784+73A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 1,590,608 control chromosomes in the GnomAD database, including 66,813 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 0.26 (5590 hom., cov: 32)
  • Exomes 𝑓: 0.29 (61223 hom.)
• Consequence: CLEC4M NM_014257.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.75

Genes affected

CLEC4M (HGNC:13523): (C-type lectin domain family 4 member M) This gene encodes a C-type lectin that functions in cell adhesion and pathogen recognition. This receptor recognizes a wide range of evolutionarily divergent pathogens with a large impact on public health, including tuberculosis mycobacteria, and viruses including Ebola, hepatitis C, HIV-1, influenza A, West Nile virus and the SARS-CoV acute respiratory syndrome coronavirus. The protein is organized into four distinct domains: a C-terminal carbohydrate recognition domain, a flexible tandem-repeat neck domain of variable length, a transmembrane region and an N-terminal cytoplasmic domain involved in internalization. This gene is closely related in terms of both sequence and function to a neighboring gene, CD209 (Gene ID: 30835), also known as DC-SIGN. The two genes differ in viral recognition and expression patterns, with this gene showing high expression in endothelial cells of the liver, lymph node and placenta. Polymorphisms in the tandem repeat neck domain are associated with resistance to SARS infection. [provided by RefSeq, May 2020]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.331 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLEC4M	NM_014257.5	c.784+73A>G		intron_variant		ENST00000327325.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLEC4M	ENST00000327325.10	c.784+73A>G		intron_variant		1	NM_014257.5	P2

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38787 AN: 152036 Hom.: 5573 Cov.: 32

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.515

Gnomad AMR AF: 0.338

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.186

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.268

GnomAD3 exomes AF: 0.279 AC: 62588 AN: 224536 Hom.: 9004 AF XY: 0.279 AC XY: 33788 AN XY: 121046

Gnomad AFR exome AF: 0.133

Gnomad AMR exome AF: 0.334

Gnomad ASJ exome AF: 0.194

Gnomad EAS exome AF: 0.188

Gnomad SAS exome AF: 0.217

Gnomad FIN exome AF: 0.309

Gnomad NFE exome AF: 0.317

Gnomad OTH exome AF: 0.294

GnomAD4 exome AF: 0.289 AC: 416008 AN: 1438454 Hom.: 61223 Cov.: 54 AF XY: 0.288 AC XY: 205690 AN XY: 713024

Gnomad4 AFR exome AF: 0.124

Gnomad4 AMR exome AF: 0.334

Gnomad4 ASJ exome AF: 0.192

Gnomad4 EAS exome AF: 0.179

Gnomad4 SAS exome AF: 0.214

Gnomad4 FIN exome AF: 0.301

Gnomad4 NFE exome AF: 0.305

Gnomad4 OTH exome AF: 0.269

GnomAD4 genome AF: 0.255 AC: 38840 AN: 152154 Hom.: 5590 Cov.: 32 AF XY: 0.255 AC XY: 18987 AN XY: 74390

Gnomad4 AFR AF: 0.133

Gnomad4 AMR AF: 0.339

Gnomad4 ASJ AF: 0.205

Gnomad4 EAS AF: 0.187

Gnomad4 SAS AF: 0.208

Gnomad4 FIN AF: 0.310

Gnomad4 NFE AF: 0.310

Gnomad4 OTH AF: 0.270

Alfa AF: 0.300 Hom.: 15012

Bravo AF: 0.254

Asia WGS AF: 0.198 AC: 689 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.045
Dann	Benign	0.30

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

Publications

LitVar

Other links and lift over

dbSNP: rs868875; hg19: chr19-7831166;