Genetic Variant CLEC16A:c.1436+10C>T (chr16-11020335-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_015226.3(CLEC16A):c.1436+10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0194 in 1,599,846 control chromosomes in the GnomAD database, including 393 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 0.016 ( 33 hom., cov: 33)

Exomes 𝑓: 0.020 ( 360 hom. )

Consequence

CLEC16A
NM_015226.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.157

Publications

3 publications found

Variant links:

Genes affected

CLEC16A (HGNC:29013): (C-type lectin domain containing 16A) This gene encodes a member of the C-type lectin domain containing family. Single nucleotide polymorphisms in introns of this gene have been associated with diabetes mellitus, multiple sclerosis and rheumatoid arthritis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]

CLEC16A Gene-Disease associations (from GenCC):

schizophrenia
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

CLEC16A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0157 (2395/152288) while in subpopulation NFE AF = 0.0238 (1619/68012). AF 95% confidence interval is 0.0228. There are 33 homozygotes in GnomAd4. There are 1210 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 33 Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015226.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CLEC16A	NM_015226.3	MANE Select	c.1436+10C>T	intron	N/A	NP_056041.1	Q2KHT3-1
CLEC16A	NM_001410905.1		c.1430+10C>T	intron	N/A	NP_001397834.1	A0A8V8TR67
CLEC16A	NM_001243403.2		c.1382+10C>T	intron	N/A	NP_001230332.1	Q2KHT3-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CLEC16A	ENST00000409790.6	TSL:5 MANE Select	c.1436+10C>T	intron	N/A	ENSP00000387122.1	Q2KHT3-1
CLEC16A	ENST00000409552.4	TSL:1	c.1382+10C>T	intron	N/A	ENSP00000386495.3	Q2KHT3-2
CLEC16A	ENST00000904405.1		c.1430+10C>T	intron	N/A	ENSP00000574464.1

Frequencies

GnomAD3 genomes

AF:

0.0157

AC:

2395

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00420

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.00850

Gnomad ASJ

AF:

0.00519

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.0389

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0238

Gnomad OTH

AF:

0.00813

GnomAD2 exomes

AF:

0.0164

AC:

3609

AN:

219940

AF XY:

0.0165

show subpopulations

Gnomad AFR exome

AF:

0.00366

Gnomad AMR exome

AF:

0.00508

Gnomad ASJ exome

AF:

0.00478

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0382

Gnomad NFE exome

AF:

0.0256

Gnomad OTH exome

AF:

0.0135

GnomAD4 exome

AF:

0.0198

AC:

28660

AN:

1447558

Hom.:

360

Cov.:

AF XY:

0.0193

AC XY:

13892

AN XY:

719216

show subpopulations

African (AFR)

AF:

0.00342

AC:

113

AN:

32998

American (AMR)

AF:

0.00601

AC:

255

AN:

42422

Ashkenazi Jewish (ASJ)

AF:

0.00461

AC:

119

AN:

25800

East Asian (EAS)

AF:

0.00

AC:

AN:

38900

South Asian (SAS)

AF:

0.00139

AC:

117

AN:

84372

European-Finnish (FIN)

AF:

0.0385

AC:

2019

AN:

52420

Middle Eastern (MID)

AF:

0.00840

AC:

AN:

5596

European-Non Finnish (NFE)

AF:

0.0227

AC:

25126

AN:

1105224

Other (OTH)

AF:

0.0144

AC:

864

AN:

59826

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

1408

2816

4223

5631

7039

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

916

1832

2748

3664

4580

<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:

0.0157

AC:

2395

AN:

152288

Hom.:

Cov.:

AF XY:

0.0163

AC XY:

1210

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.00419

AC:

174

AN:

41572

American (AMR)

AF:

0.00849

AC:

130

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00519

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5172

South Asian (SAS)

AF:

0.00186

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.0389

AC:

413

AN:

10604

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0238

AC:

1619

AN:

68012

Other (OTH)

AF:

0.00805

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

126

252

379

505

631

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

130

<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:

0.0161

Hom.:

Bravo

AF:

0.0128

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

6.4

(source)

DANN

Benign

0.78

PhyloP100

-0.16

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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