16-11003298-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP6_Very_Strong BP7

The NM_015226.3(CLEC16A):c.1296G>A(p.Glu432=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00193 in 1,610,498 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0016 (1 hom., cov: 31)
  • Exomes 𝑓: 0.0020 (6 hom.)
• Consequence: CLEC16A NM_015226.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.33

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]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 16-11003298-G-A is Benign according to our data. Variant chr16-11003298-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 711595.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.33 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLEC16A	NM_015226.3	c.1296G>A	p.Glu432=	synonymous_variant	11/24	ENST00000409790.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLEC16A	ENST00000409790.6	c.1296G>A	p.Glu432=	synonymous_variant	11/24	5	NM_015226.3	A1
CLEC16A	ENST00000409552.4	c.1249+41G>A		intron_variant		1
CLEC16A	ENST00000703130.1	c.1290G>A	p.Glu430=	synonymous_variant	10/23			P4
CLEC16A	ENST00000494853.1	n.771G>A		non_coding_transcript_exon_variant	6/8	3

Frequencies

GnomAD3 genomes AF: 0.00158 AC: 241 AN: 152108 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.000410

Gnomad AMI AF: 0.0714

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000659

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00215

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.00158 AC: 393 AN: 248010 Hom.: 0 AF XY: 0.00165 AC XY: 222 AN XY: 134652

Gnomad AFR exome AF: 0.000712

Gnomad AMR exome AF: 0.000174

Gnomad ASJ exome AF: 0.0000998

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000490

Gnomad FIN exome AF: 0.00121

Gnomad NFE exome AF: 0.00289

Gnomad OTH exome AF: 0.00166

GnomAD4 exome AF: 0.00197 AC: 2870 AN: 1458272 Hom.: 6 Cov.: 31 AF XY: 0.00195 AC XY: 1416 AN XY: 725364

Gnomad4 AFR exome AF: 0.000330

Gnomad4 AMR exome AF: 0.000269

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000418

Gnomad4 FIN exome AF: 0.00157

Gnomad4 NFE exome AF: 0.00237

Gnomad4 OTH exome AF: 0.00148

GnomAD4 genome AF: 0.00158 AC: 241 AN: 152226 Hom.: 1 Cov.: 31 AF XY: 0.00168 AC XY: 125 AN XY: 74440

Gnomad4 AFR AF: 0.000409

Gnomad4 AMR AF: 0.000327

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000659

Gnomad4 NFE AF: 0.00215

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.00198 Hom.: 0

Bravo AF: 0.00178

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00229

EpiControl AF: 0.00178

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Dec 31, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Apr 01, 2022	CLEC16A: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
Cadd	Benign	9.1
Dann	Benign	0.64

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

LitVar

Other links and lift over

dbSNP: rs45464291; hg19: chr16-11097155;