chr19-7766121-A-G

Position:

• chr19-7766121-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_014257.5(CLEC4M):​c.698A>G​(p.Gln233Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000259 in 1,452,334 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0034 (5 hom., cov: 29)
  • Exomes 𝑓: 0.00026 (2 hom.)
  • Failed GnomAD Quality Control
• Consequence: CLEC4M NM_014257.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.18

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]

CLEC4M (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008916527).
• BP6: Variant 19-7766121-A-G is Benign according to our data. Variant chr19-7766121-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2649180.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLEC4M	NM_014257.5	c.698A>G	p.Gln233Arg	missense_variant	4/7	ENST00000327325.10	NP_055072.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLEC4M	ENST00000327325.10	c.698A>G	p.Gln233Arg	missense_variant	4/7	1	NM_014257.5	ENSP00000316228.4

Frequencies

GnomAD3 genomes AF: 0.00343 AC: 498 AN: 145000 Hom.: 5 Cov.: 29

Gnomad AFR AF: 0.0108

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00103

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00144

Gnomad SAS AF: 0.000443

Gnomad FIN AF: 0.000816

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000565

Gnomad OTH AF: 0.00252

GnomAD3 exomes AF: 0.000412 AC: 103 AN: 249768 Hom.: 1 AF XY: 0.000304 AC XY: 41 AN XY: 135028

Gnomad AFR exome AF: 0.00165

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.0000996

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000419

Gnomad NFE exome AF: 0.000539

Gnomad OTH exome AF: 0.000329

GnomAD4 exome AF: 0.000259 AC: 376 AN: 1452334 Hom.: 2 Cov.: 31 AF XY: 0.000295 AC XY: 213 AN XY: 722670

Gnomad4 AFR exome AF: 0.00262

Gnomad4 AMR exome AF: 0.000113

Gnomad4 ASJ exome AF: 0.000115

Gnomad4 EAS exome AF: 0.0000757

Gnomad4 SAS exome AF: 0.0000580

Gnomad4 FIN exome AF: 0.000169

Gnomad4 NFE exome AF: 0.000215

Gnomad4 OTH exome AF: 0.000433

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00345 AC: 500 AN: 145100 Hom.: 5 Cov.: 29 AF XY: 0.00360 AC XY: 255 AN XY: 70808

Gnomad4 AFR AF: 0.0108

Gnomad4 AMR AF: 0.00103

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00145

Gnomad4 SAS AF: 0.000444

Gnomad4 FIN AF: 0.000816

Gnomad4 NFE AF: 0.000565

Gnomad4 OTH AF: 0.00249

Alfa AF: 0.00420 Hom.: 1

ExAC AF: 0.00314 AC: 381

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

CLEC4M: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	4.2
DANN	Benign	0.83
DEOGEN2	Benign	0.022	.;.;T;.;T;.;.
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.45	T;T;T;T;T;T;T
MetaRNN	Benign	0.0089	T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.66	.;.;.;.;N;.;.
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.48	N;.;N;D;N;.;.
REVEL	Benign	0.027
Sift	Benign	0.49	T;.;T;T;T;.;.
Sift4G	Benign	0.51	T;T;T;T;T;T;T
Polyphen		0.0	.;B;B;.;B;B;.
Vest4		0.079
MVP		0.17
MPC		0.26
ClinPred		0.011	T
GERP RS		1.4
Varity_R		0.061
gMVP		0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs144783051; hg19: chr19-7831007; COSMIC: COSV50216989; COSMIC: COSV50216989;