rs12935657

Variant names:

• chr16-11125184-G-A
• rs12935657
• NM_015226.3:c.2474-795G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-11125184-G-A
• chr16-11125184-G-T

Variant summary

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

The NM_015226.3(CLEC16A):​c.2474-795G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 152,138 control chromosomes in the GnomAD database, including 3,265 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 0.19 (3265 hom., cov: 32)
• Consequence: CLEC16A NM_015226.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.809
• Publications: 22 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.25 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.2474-795G>A		intron	N/A	NP_056041.1
	CLEC16A	NM_001410905.1		c.2468-795G>A		intron	N/A	NP_001397834.1
	CLEC16A	NM_001243403.2		c.2420-795G>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.2474-795G>A		intron	N/A	ENSP00000387122.1
	CLEC16A	ENST00000409552.4	TSL:1	c.2420-795G>A		intron	N/A	ENSP00000386495.3
	CLEC16A	ENST00000703130.1		c.2468-795G>A		intron	N/A	ENSP00000515187.1

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28168 AN: 152020 Hom.: 3266 Cov.: 32

Gnomad AFR AF: 0.0541

Gnomad AMI AF: 0.273

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.354

Gnomad EAS AF: 0.0619

Gnomad SAS AF: 0.249

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.253

Gnomad OTH AF: 0.217

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

GnomAD4 genome AF: 0.185 AC: 28155 AN: 152138 Hom.: 3265 Cov.: 32 AF XY: 0.184 AC XY: 13678 AN XY: 74380

African (AFR) AF: 0.0539 AC: 2239 AN: 41512

American (AMR) AF: 0.184 AC: 2814 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.354 AC: 1230 AN: 3470

East Asian (EAS) AF: 0.0620 AC: 322 AN: 5192

South Asian (SAS) AF: 0.250 AC: 1209 AN: 4830

European-Finnish (FIN) AF: 0.224 AC: 2363 AN: 10566

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.253 AC: 17200 AN: 67964

Other (OTH) AF: 0.215 AC: 454 AN: 2114

Alfa AF: 0.144 Hom.: 514

Bravo AF: 0.173

Asia WGS AF: 0.153 AC: 533 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.0090
DANN	Benign	0.93
PhyloP100		-0.81
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: rs12935657; hg19: chr16-11219041;