chr16-10970464-T-C

Variant names:

• chr16-10970464-T-C
• rs12921922
• NM_015226.3:c.493-661T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.216 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.493-661T>C		intron	N/A	NP_056041.1
	CLEC16A	NM_001410905.1		c.493-661T>C		intron	N/A	NP_001397834.1
	CLEC16A	NM_001243403.2		c.493-661T>C		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.493-661T>C		intron	N/A	ENSP00000387122.1
	CLEC16A	ENST00000409552.4	TSL:1	c.493-661T>C		intron	N/A	ENSP00000386495.3
	CLEC16A	ENST00000703130.1		c.493-661T>C		intron	N/A	ENSP00000515187.1

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

African (AFR) AF: 0.0435 AC: 1808 AN: 41570

American (AMR) AF: 0.160 AC: 2448 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.275 AC: 955 AN: 3468

East Asian (EAS) AF: 0.104 AC: 538 AN: 5190

South Asian (SAS) AF: 0.227 AC: 1095 AN: 4830

European-Finnish (FIN) AF: 0.183 AC: 1936 AN: 10598

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.212 AC: 14429 AN: 67996

Other (OTH) AF: 0.179 AC: 378 AN: 2108

Alfa AF: 0.117 Hom.: 306

Bravo AF: 0.147

Asia WGS AF: 0.177 AC: 615 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.9
DANN	Benign	0.76
PhyloP100		-0.23
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: rs12921922; hg19: chr16-11064321;