rs12921922

Positions:

• chr16-10970464-T-C
• chr16-10970464-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015226.3(CLEC16A):​c.493-661T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 152,266 control chromosomes in the GnomAD database, including 2,338 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 0.16 (2338 hom., cov: 33)
• Consequence: CLEC16A NM_015226.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.232

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLEC16A	NM_015226.3	c.493-661T>C		intron_variant		ENST00000409790.6	NP_056041.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLEC16A	ENST00000409790.6	c.493-661T>C		intron_variant		5	NM_015226.3	ENSP00000387122	A1
CLEC16A	ENST00000409552.4	c.493-661T>C		intron_variant		1		ENSP00000386495
CLEC16A	ENST00000703130.1	c.493-661T>C		intron_variant				ENSP00000515187	P4

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23856 AN: 152148 Hom.: 2335 Cov.: 33

Gnomad AFR AF: 0.0437

Gnomad AMI AF: 0.229

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.275

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.177

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

GnomAD4 genome AF: 0.157 AC: 23856 AN: 152266 Hom.: 2338 Cov.: 33 AF XY: 0.157 AC XY: 11666 AN XY: 74460

Gnomad4 AFR AF: 0.0435

Gnomad4 AMR AF: 0.160

Gnomad4 ASJ AF: 0.275

Gnomad4 EAS AF: 0.104

Gnomad4 SAS AF: 0.227

Gnomad4 FIN AF: 0.183

Gnomad4 NFE AF: 0.212

Gnomad4 OTH AF: 0.179

Alfa AF: 0.114 Hom.: 267

Bravo AF: 0.147

Asia WGS AF: 0.177 AC: 615 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.9
DANN	Benign	0.76

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: rs12921922; hg19: chr16-11064321;