Genetic Variant CLEC16A:c.344-7C>T (chr16-10969154-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_015226.3(CLEC16A):c.344-7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 1,594,830 control chromosomes in the GnomAD database, including 19,051 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.21 ( 4478 hom., cov: 31)

Exomes 𝑓: 0.13 ( 14573 hom. )

Consequence

CLEC16A
NM_015226.3 splice_region, intron

Scores

Splicing: ADA: 0.00002818

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.138

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 links:

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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=-0.77).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.4 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLEC16A	NM_015226.3 link	c.344-7C>T		splice_region_variant, intron_variant	Intron 3 of 23	ENST00000409790.6	NP_056041.1	Q2KHT3-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CLEC16A	ENST00000409790.6 link	c.344-7C>T	splice_region_variant, intron_variant	Intron 3 of 23	5	NM_015226.3	ENSP00000387122.1	Q2KHT3-1
CLEC16A	ENST00000409552.4 link	c.344-7C>T	splice_region_variant, intron_variant	Intron 3 of 20	1		ENSP00000386495.3	Q2KHT3-2
CLEC16A	ENST00000703130.1 link	c.344-7C>T	splice_region_variant, intron_variant	Intron 3 of 22			ENSP00000515187.1	A0A8V8TR67

Frequencies

GnomAD3 genomes

AF:

0.210

AC:

31828

AN:

151694

Hom.:

4460

Cov.:

show subpopulations

Gnomad AFR

AF:

0.405

Gnomad AMI

AF:

0.107

Gnomad AMR

AF:

0.148

Gnomad ASJ

AF:

0.173

Gnomad EAS

AF:

0.111

Gnomad SAS

AF:

0.145

Gnomad FIN

AF:

0.153

Gnomad MID

AF:

0.190

Gnomad NFE

AF:

0.130

Gnomad OTH

AF:

0.198

GnomAD2 exomes

AF:

0.144

AC:

34216

AN:

237476

AF XY:

0.143

show subpopulations

Gnomad AFR exome

AF:

0.407

Gnomad AMR exome

AF:

0.104

Gnomad ASJ exome

AF:

0.161

Gnomad EAS exome

AF:

0.109

Gnomad FIN exome

AF:

0.142

Gnomad NFE exome

AF:

0.125

Gnomad OTH exome

AF:

0.136

GnomAD4 exome

AF:

0.133

AC:

192522

AN:

1443018

Hom.:

14573

Cov.:

AF XY:

0.134

AC XY:

96158

AN XY:

718350

show subpopulations

Gnomad4 AFR exome

AF:

0.411

AC:

13189

AN:

32058

Gnomad4 AMR exome

AF:

0.107

AC:

4396

AN:

41122

Gnomad4 ASJ exome

AF:

0.162

AC:

4184

AN:

25784

Gnomad4 EAS exome

AF:

0.0824

AC:

3254

AN:

39478

Gnomad4 SAS exome

AF:

0.149

AC:

12515

AN:

84254

Gnomad4 FIN exome

AF:

0.141

AC:

7445

AN:

52750

Gnomad4 NFE exome

AF:

0.125

AC:

138028

AN:

1102380

Gnomad4 Remaining exome

AF:

0.143

AC:

8511

AN:

59652

Heterozygous variant carriers

6611

13222

19833

26444

33055

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

5122

10244

15366

20488

25610

<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:

0.210

AC:

31893

AN:

151812

Hom.:

4478

Cov.:

AF XY:

0.207

AC XY:

15382

AN XY:

74202

show subpopulations

Gnomad4 AFR

AF:

0.405

AC:

0.405052

AN:

0.405052

Gnomad4 AMR

AF:

0.147

AC:

0.147495

AN:

0.147495

Gnomad4 ASJ

AF:

0.173

AC:

0.17311

AN:

0.17311

Gnomad4 EAS

AF:

0.111

AC:

0.111003

AN:

0.111003

Gnomad4 SAS

AF:

0.145

AC:

0.144846

AN:

0.144846

Gnomad4 FIN

AF:

0.153

AC:

0.152686

AN:

0.152686

Gnomad4 NFE

AF:

0.130

AC:

0.13017

AN:

0.13017

Gnomad4 OTH

AF:

0.200

AC:

0.200474

AN:

0.200474

Heterozygous variant carriers

1143

2286

3428

4571

5714

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

316

632

948

1264

1580

<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:

0.153

Hom.:

4288

Bravo

AF:

0.218

Asia WGS

AF:

0.146

AC:

505

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

5.6

DANN

Benign

0.55

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=99/1

polymorphism (auto)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000028

dbscSNV1_RF

Benign

0.0

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over