rs12928537

Variant names:

• chr16-11097543-G-A
• rs12928537
• NM_015226.3:c.2117-23072G>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.2117-23072G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 152,036 control chromosomes in the GnomAD database, including 8,499 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 0.33 (8499 hom., cov: 32)
• Consequence: CLEC16A NM_015226.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.273
• Publications: 9 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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLEC16A	NM_015226.3	MANE Select	c.2117-23072G>A		intron	N/A	NP_056041.1
	CLEC16A	NM_001410905.1		c.2111-23072G>A		intron	N/A	NP_001397834.1
	CLEC16A	NM_001243403.2		c.2063-23072G>A		intron	N/A	NP_001230332.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLEC16A	ENST00000409790.6	TSL:5 MANE Select	c.2117-23072G>A		intron	N/A	ENSP00000387122.1
	CLEC16A	ENST00000409552.4	TSL:1	c.2063-23072G>A		intron	N/A	ENSP00000386495.3
	CLEC16A	ENST00000703130.1		c.2111-23072G>A		intron	N/A	ENSP00000515187.1

Frequencies

GnomAD3 genomes AF: 0.333 AC: 50585 AN: 151918 Hom.: 8469 Cov.: 32

Gnomad AFR AF: 0.363

Gnomad AMI AF: 0.229

Gnomad AMR AF: 0.279

Gnomad ASJ AF: 0.412

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.394

Gnomad FIN AF: 0.328

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.341

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

GnomAD4 genome AF: 0.333 AC: 50667 AN: 152036 Hom.: 8499 Cov.: 32 AF XY: 0.332 AC XY: 24661 AN XY: 74310

African (AFR) AF: 0.364 AC: 15090 AN: 41466

American (AMR) AF: 0.279 AC: 4263 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.412 AC: 1428 AN: 3466

East Asian (EAS) AF: 0.217 AC: 1125 AN: 5176

South Asian (SAS) AF: 0.395 AC: 1898 AN: 4804

European-Finnish (FIN) AF: 0.328 AC: 3462 AN: 10560

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.329 AC: 22354 AN: 67962

Other (OTH) AF: 0.345 AC: 728 AN: 2108

Alfa AF: 0.321 Hom.: 12376

Bravo AF: 0.328

Asia WGS AF: 0.332 AC: 1155 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	9.1
DANN	Benign	0.60
PhyloP100		-0.27
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: rs12928537; hg19: chr16-11191400;