rs12931878

Variant names:

• chr16-10948337-A-G
• rs12931878
• NM_015226.3:c.80+3540A>G

Variant summary

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

The NM_015226.3(CLEC16A):​c.80+3540A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 152,236 control chromosomes in the GnomAD database, including 1,992 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 0.14 (1992 hom., cov: 33)
• Consequence: CLEC16A NM_015226.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0480
• Publications: 20 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLEC16A	NM_015226.3	c.80+3540A>G		intron_variant	Intron 1 of 23	ENST00000409790.6	NP_056041.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLEC16A	ENST00000409790.6	c.80+3540A>G		intron_variant	Intron 1 of 23	5	NM_015226.3	ENSP00000387122.1
CLEC16A	ENST00000409552.4	c.80+3540A>G		intron_variant	Intron 1 of 20	1		ENSP00000386495.3
CLEC16A	ENST00000703130.1	c.80+3540A>G		intron_variant	Intron 1 of 22			ENSP00000515187.1

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22048 AN: 152116 Hom.: 1991 Cov.: 33

Gnomad AFR AF: 0.0490

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.305

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.180

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

GnomAD4 genome AF: 0.145 AC: 22046 AN: 152236 Hom.: 1992 Cov.: 33 AF XY: 0.144 AC XY: 10713 AN XY: 74442

African (AFR) AF: 0.0488 AC: 2030 AN: 41570

American (AMR) AF: 0.145 AC: 2219 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.305 AC: 1060 AN: 3472

East Asian (EAS) AF: 0.109 AC: 567 AN: 5190

South Asian (SAS) AF: 0.223 AC: 1078 AN: 4832

European-Finnish (FIN) AF: 0.156 AC: 1645 AN: 10576

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.189 AC: 12818 AN: 67984

Other (OTH) AF: 0.181 AC: 384 AN: 2116

Alfa AF: 0.174 Hom.: 1309

Bravo AF: 0.137

Asia WGS AF: 0.184 AC: 641 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.4
DANN	Benign	0.67
PhyloP100		0.048
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: rs12931878; hg19: chr16-11042194;