rs876457

Variant names:

• chr16-11049869-G-A
• rs876457
• NM_015226.3:c.1867-1644G>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.1867-1644G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0894 in 152,268 control chromosomes in the GnomAD database, including 654 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 0.089 (654 hom., cov: 33)
• Consequence: CLEC16A NM_015226.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.317
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.123 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.1867-1644G>A		intron	N/A	NP_056041.1
	CLEC16A	NM_001410905.1		c.1861-1644G>A		intron	N/A	NP_001397834.1
	CLEC16A	NM_001243403.2		c.1813-1644G>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.1867-1644G>A		intron	N/A	ENSP00000387122.1
	CLEC16A	ENST00000409552.4	TSL:1	c.1813-1644G>A		intron	N/A	ENSP00000386495.3
	CLEC16A	ENST00000703130.1		c.1861-1644G>A		intron	N/A	ENSP00000515187.1

Frequencies

GnomAD3 genomes AF: 0.0894 AC: 13605 AN: 152150 Hom.: 652 Cov.: 33

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.0859

Gnomad ASJ AF: 0.0588

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.0434

Gnomad FIN AF: 0.0647

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0749

Gnomad OTH AF: 0.0913

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

GnomAD4 genome AF: 0.0894 AC: 13609 AN: 152268 Hom.: 654 Cov.: 33 AF XY: 0.0890 AC XY: 6625 AN XY: 74440

African (AFR) AF: 0.125 AC: 5210 AN: 41534

American (AMR) AF: 0.0857 AC: 1311 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0588 AC: 204 AN: 3472

East Asian (EAS) AF: 0.111 AC: 575 AN: 5174

South Asian (SAS) AF: 0.0435 AC: 210 AN: 4832

European-Finnish (FIN) AF: 0.0647 AC: 686 AN: 10610

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0748 AC: 5091 AN: 68020

Other (OTH) AF: 0.0918 AC: 194 AN: 2114

Alfa AF: 0.0775 Hom.: 243

Bravo AF: 0.0938

Asia WGS AF: 0.0930 AC: 321 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.4
DANN	Benign	0.52
PhyloP100		-0.32
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: rs876457; hg19: chr16-11143726;