Genetic Variant CLEC11A:p.Ala278ProfsTer129 (chr19-50725314-C-CGCCCA) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_002975.3(CLEC11A):c.827_831dupCCAGC(p.Ala278ProfsTer129) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00198 in 1,611,922 control chromosomes in the GnomAD database, including 14 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0015 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0020 ( 12 hom. )

Consequence

CLEC11A
NM_002975.3 frameshift

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0370

Publications

0 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: Likely_benign. The variant received -6 ACMG points.

BP6

Variant 19-50725314-C-CGCCCA is Benign according to our data. Variant chr19-50725314-C-CGCCCA is described in CliVar as Likely_benign. Clinvar id is 785833.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-50725314-C-CGCCCA is described in CliVar as Likely_benign. Clinvar id is 785833.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-50725314-C-CGCCCA is described in CliVar as Likely_benign. Clinvar id is 785833.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-50725314-C-CGCCCA is described in CliVar as Likely_benign. Clinvar id is 785833.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-50725314-C-CGCCCA is described in CliVar as Likely_benign. Clinvar id is 785833.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-50725314-C-CGCCCA is described in CliVar as Likely_benign. Clinvar id is 785833.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLEC11A	NM_002975.3 link	c.827_831dupCCAGC	p.Ala278ProfsTer129	frameshift_variant	Exon 4 of 4	ENST00000250340.9	NP_002966.1	Q9Y240

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLEC11A	ENST00000250340.9 link	c.827_831dupCCAGC	p.Ala278ProfsTer129	frameshift_variant	Exon 4 of 4	1	NM_002975.3	ENSP00000250340.3		Q9Y240
CLEC11A	ENST00000599973.1 link	c.876_880dupCCAGC	p.Arg294ProfsTer49	frameshift_variant	Exon 4 of 4	1		ENSP00000471075.1		M0R081

Frequencies

GnomAD3 genomes

AF:

0.00156

AC:

237

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00124

Gnomad ASJ

AF:

0.00778

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00257

Gnomad OTH

AF:

0.00192

GnomAD2 exomes

AF:

0.00166

AC:

391

AN:

236204

AF XY:

0.00174

show subpopulations

Gnomad AFR exome

AF:

0.000144

Gnomad AMR exome

AF:

0.00158

Gnomad ASJ exome

AF:

0.00723

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00234

Gnomad OTH exome

AF:

0.00328

GnomAD4 exome

AF:

0.00203

AC:

2956

AN:

1459606

Hom.:

Cov.:

AF XY:

0.00201

AC XY:

1461

AN XY:

726132

show subpopulations

African (AFR)

AF:

0.000269

AC:

AN:

33460

American (AMR)

AF:

0.00166

AC:

AN:

44636

Ashkenazi Jewish (ASJ)

AF:

0.00794

AC:

207

AN:

26062

East Asian (EAS)

AF:

0.00

AC:

AN:

39674

South Asian (SAS)

AF:

0.000128

AC:

AN:

86144

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52298

Middle Eastern (MID)

AF:

0.00608

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.00224

AC:

2485

AN:

1111382

Other (OTH)

AF:

0.00224

AC:

135

AN:

60192

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

181

361

542

722

903

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

200

300

400

500

<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:

0.00155

AC:

236

AN:

152316

Hom.:

Cov.:

AF XY:

0.00144

AC XY:

107

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.000192

AC:

AN:

41570

American (AMR)

AF:

0.00124

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00778

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00257

AC:

175

AN:

68024

Other (OTH)

AF:

0.00190

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

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:

0.00154

Hom.:

EpiCase

AF:

0.00360

EpiControl

AF:

0.00380

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Mar 29, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.037

Mutation Taster

=140/60

polymorphism

(source)

Splicing

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over