chr19-7766280-A-G

Variant names:

• chr19-7766280-A-G
• rs868875
• NM_014257.5:c.784+73A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 26 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014257.5. 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
	CLEC4M	NM_014257.5	MANE Select	c.784+73A>G		intron	N/A	NP_055072.3
	CLEC4M	NM_001416369.1		c.700+73A>G		intron	N/A	NP_001403298.1	A0A7P0MMK7
	CLEC4M	NM_001416370.1		c.616+73A>G		intron	N/A	NP_001403299.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLEC4M	ENST00000327325.10	TSL:1 MANE Select	c.784+73A>G		intron	N/A	ENSP00000316228.4	Q9H2X3-1
	CLEC4M	ENST00000596363.5	TSL:1	c.700+73A>G		intron	N/A	ENSP00000471125.1	Q9H2X3-9
	CLEC4M	ENST00000598879.5	TSL:1	n.857A>G		non_coding_transcript_exon	Exon 4 of 5

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

GnomAD2 exomes AF: 0.279 AC: 62588 AN: 224536 AF XY: 0.279

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 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

African (AFR) AF: 0.124 AC: 4098 AN: 33024

American (AMR) AF: 0.334 AC: 14002 AN: 41890

Ashkenazi Jewish (ASJ) AF: 0.192 AC: 4851 AN: 25330

East Asian (EAS) AF: 0.179 AC: 7058 AN: 39352

South Asian (SAS) AF: 0.214 AC: 18027 AN: 84224

European-Finnish (FIN) AF: 0.301 AC: 14861 AN: 49354

Middle Eastern (MID) AF: 0.250 AC: 1405 AN: 5618

European-Non Finnish (NFE) AF: 0.305 AC: 335683 AN: 1100146

Other (OTH) AF: 0.269 AC: 16023 AN: 59516

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

African (AFR) AF: 0.133 AC: 5506 AN: 41530

American (AMR) AF: 0.339 AC: 5174 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.205 AC: 712 AN: 3468

East Asian (EAS) AF: 0.187 AC: 968 AN: 5182

South Asian (SAS) AF: 0.208 AC: 1003 AN: 4832

European-Finnish (FIN) AF: 0.310 AC: 3282 AN: 10584

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.310 AC: 21072 AN: 67974

Other (OTH) AF: 0.270 AC: 571 AN: 2112

Alfa AF: 0.292 Hom.: 30771

Bravo AF: 0.254

Asia WGS AF: 0.198 AC: 689 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.045
DANN	Benign	0.30
PhyloP100		-1.8
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: rs868875; hg19: chr19-7831166;