Genetic Variant CLEC11A:p.Gly165Asp (chr19-50724569-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_002975.3(CLEC11A):c.494G>A(p.Gly165Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000325 in 1,455,316 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G165V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00066 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00029 ( 3 hom. )

Consequence

CLEC11A
NM_002975.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.361

Publications

1 publications found

Variant links:

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]

CLEC11A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0052238405).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

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.494G>A	p.Gly165Asp	missense	Exon 3 of 4	NP_002966.1	Q9Y240

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CLEC11A	ENST00000250340.9	TSL:1 MANE Select	c.494G>A	p.Gly165Asp	missense	Exon 3 of 4	ENSP00000250340.3	Q9Y240
CLEC11A	ENST00000599973.1	TSL:1	c.494G>A	p.Gly165Asp	missense	Exon 3 of 4	ENSP00000471075.1	M0R081
CLEC11A	ENST00000883282.1		c.485G>A	p.Gly162Asp	missense	Exon 3 of 4	ENSP00000553341.1

Frequencies

GnomAD3 genomes

AF:

0.000663

AC:

101

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000289

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00412

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.000955

GnomAD2 exomes

AF:

0.000830

AC:

AN:

71092

AF XY:

0.000775

show subpopulations

Gnomad AFR exome

AF:

0.000460

Gnomad AMR exome

AF:

0.00279

Gnomad ASJ exome

AF:

0.00236

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000196

Gnomad OTH exome

AF:

0.00264

GnomAD4 exome

AF:

0.000286

AC:

372

AN:

1302968

Hom.:

Cov.:

AF XY:

0.000317

AC XY:

202

AN XY:

636698

show subpopulations

African (AFR)

AF:

0.00117

AC:

AN:

26426

American (AMR)

AF:

0.00223

AC:

AN:

23334

Ashkenazi Jewish (ASJ)

AF:

0.00142

AC:

AN:

21080

East Asian (EAS)

AF:

0.00

AC:

AN:

32000

South Asian (SAS)

AF:

0.000117

AC:

AN:

68198

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32230

Middle Eastern (MID)

AF:

0.00809

AC:

AN:

4202

European-Non Finnish (NFE)

AF:

0.000163

AC:

170

AN:

1041356

Other (OTH)

AF:

0.000868

AC:

AN:

54142

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

101

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000663

AC:

101

AN:

152348

Hom.:

Cov.:

AF XY:

0.000792

AC XY:

AN XY:

74496

show subpopulations

African (AFR)

AF:

0.000289

AC:

AN:

41592

American (AMR)

AF:

0.00411

AC:

AN:

15314

Ashkenazi Jewish (ASJ)

AF:

0.00173

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000265

AC:

AN:

68020

Other (OTH)

AF:

0.000945

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000517

Hom.:

Bravo

AF:

0.000827

ExAC

AF:

0.000258

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.64

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.055

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.98

FATHMM_MKL

Benign

0.46

LIST_S2

Benign

0.44

MetaRNN

Benign

0.0052

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

PhyloP100

0.36

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-0.17

REVEL

Benign

0.079

Sift

Benign

0.46

Sift4G

Benign

0.70

Polyphen

0.0

Vest4

0.098

MVP

0.47

MPC

0.50

ClinPred

0.0088

GERP RS

-3.6

Varity_R

0.080

gMVP

0.41

Mutation Taster

=99/1

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over