19-50724046-G-C

Variant names:

• chr19-50724046-G-C
• rs202169240
• NM_002975.3:c.289G>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_002975.3(CLEC11A):​c.289G>C​(p.Gly97Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000388 in 1,612,398 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00039 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00039 (0 hom.)
• Consequence: CLEC11A NM_002975.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0560
• Publications: 1 publications found

Genes affected

CLEC11A (HGNC:10576): (C-type lectin domain containing 11A) This gene encodes a member of the C-type lectin superfamily. The encoded protein is a secreted sulfated glycoprotein and functions as a growth factor for primitive hematopoietic progenitor cells. An alternative splice variant has been described but its biological nature has not been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007265687).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002975.3. 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
	CLEC11A	NM_002975.3	MANE Select	c.289G>C	p.Gly97Arg	missense	Exon 2 of 4	NP_002966.1	Q9Y240

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLEC11A	ENST00000250340.9	TSL:1 MANE Select	c.289G>C	p.Gly97Arg	missense	Exon 2 of 4	ENSP00000250340.3	Q9Y240
	CLEC11A	ENST00000599973.1	TSL:1	c.289G>C	p.Gly97Arg	missense	Exon 2 of 4	ENSP00000471075.1	M0R081
	CLEC11A	ENST00000883282.1		c.280G>C	p.Gly94Arg	missense	Exon 2 of 4	ENSP00000553341.1

Frequencies

GnomAD3 genomes AF: 0.000388 AC: 59 AN: 151934 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000472

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000692

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000532 AC: 132 AN: 248124 AF XY: 0.000498

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00230

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000324

Gnomad NFE exome AF: 0.000902

Gnomad OTH exome AF: 0.000329

GnomAD4 exome AF: 0.000388 AC: 566 AN: 1460464 Hom.: 0 Cov.: 31 AF XY: 0.000367 AC XY: 267 AN XY: 726606

African (AFR) AF: 0.0000299 AC: 1 AN: 33452

American (AMR) AF: 0.00 AC: 0 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.00165 AC: 43 AN: 26106

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39678

South Asian (SAS) AF: 0.00 AC: 0 AN: 86216

European-Finnish (FIN) AF: 0.000506 AC: 27 AN: 53388

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.000429 AC: 476 AN: 1110824

Other (OTH) AF: 0.000298 AC: 18 AN: 60340

GnomAD4 genome AF: 0.000388 AC: 59 AN: 151934 Hom.: 0 Cov.: 31 AF XY: 0.000270 AC XY: 20 AN XY: 74196

African (AFR) AF: 0.00 AC: 0 AN: 41354

American (AMR) AF: 0.0000655 AC: 1 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.000472 AC: 5 AN: 10590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000692 AC: 47 AN: 67948

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.000873 Hom.: 0

Bravo AF: 0.000302

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000698 AC: 6

ExAC AF: 0.000717 AC: 87

EpiCase AF: 0.000327

EpiControl AF: 0.000297

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	6.5
DANN	Benign	0.82
DEOGEN2	Benign	0.071	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.048	N
LIST_S2	Benign	0.24	T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.0073	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.69	N
PhyloP100		-0.056
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.060	N
REVEL	Benign	0.029
Sift	Benign	0.30	T
Sift4G	Benign	0.57	T
Polyphen		0.0010	B
Vest4		0.081
MVP		0.27
MPC		0.46
ClinPred		0.028	T
GERP RS		-4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.038
gMVP		0.059
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs202169240; hg19: chr19-51227303; COSMIC: COSV107224427;