rs12935413

Variant names:

• chr16-11116590-G-A
• rs12935413
• NM_015226.3:c.2117-4025G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015226.3(CLEC16A):​c.2117-4025G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 151,910 control chromosomes in the GnomAD database, including 8,781 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 0.34 (8781 hom., cov: 31)
• Consequence: CLEC16A NM_015226.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49
• Publications: 21 publications found

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)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLEC16A	NM_015226.3	c.2117-4025G>A		intron_variant	Intron 19 of 23	ENST00000409790.6	NP_056041.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLEC16A	ENST00000409790.6	c.2117-4025G>A		intron_variant	Intron 19 of 23	5	NM_015226.3	ENSP00000387122.1

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51320 AN: 151790 Hom.: 8758 Cov.: 31

Gnomad AFR AF: 0.318

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.439

Gnomad EAS AF: 0.230

Gnomad SAS AF: 0.393

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.376

Gnomad NFE AF: 0.358

Gnomad OTH AF: 0.351

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.338 AC: 51384 AN: 151910 Hom.: 8781 Cov.: 31 AF XY: 0.336 AC XY: 24950 AN XY: 74252

African (AFR) AF: 0.318 AC: 13170 AN: 41390

American (AMR) AF: 0.297 AC: 4539 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.439 AC: 1524 AN: 3470

East Asian (EAS) AF: 0.231 AC: 1193 AN: 5172

South Asian (SAS) AF: 0.395 AC: 1899 AN: 4808

European-Finnish (FIN) AF: 0.340 AC: 3589 AN: 10544

Middle Eastern (MID) AF: 0.373 AC: 109 AN: 292

European-Non Finnish (NFE) AF: 0.358 AC: 24350 AN: 67954

Other (OTH) AF: 0.354 AC: 745 AN: 2104

Alfa AF: 0.329 Hom.: 3659

Bravo AF: 0.333

Asia WGS AF: 0.337 AC: 1173 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.25
DANN	Benign	0.63
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12935413; hg19: chr16-11210447; COSMIC: COSV68502204;