16-10954493-A-G

Variant names:

• chr16-10954493-A-G
• rs1035089
• NM_015226.3:c.81-3289A>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.81-3289A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.611 in 152,042 control chromosomes in the GnomAD database, including 29,792 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 0.61 (29792 hom., cov: 32)
• Consequence: CLEC16A NM_015226.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.259
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.798 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLEC16A	NM_015226.3	MANE Select	c.81-3289A>G		intron	N/A	NP_056041.1	Q2KHT3-1
	CLEC16A	NM_001410905.1		c.81-3289A>G		intron	N/A	NP_001397834.1	A0A8V8TR67
	CLEC16A	NM_001243403.2		c.81-3289A>G		intron	N/A	NP_001230332.1	Q2KHT3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLEC16A	ENST00000409790.6	TSL:5 MANE Select	c.81-3289A>G		intron	N/A	ENSP00000387122.1	Q2KHT3-1
	CLEC16A	ENST00000409552.4	TSL:1	c.81-3289A>G		intron	N/A	ENSP00000386495.3	Q2KHT3-2
	CLEC16A	ENST00000904405.1		c.81-3289A>G		intron	N/A	ENSP00000574464.1

Frequencies

GnomAD3 genomes AF: 0.610 AC: 92732 AN: 151922 Hom.: 29742 Cov.: 32

Gnomad AFR AF: 0.805

Gnomad AMI AF: 0.595

Gnomad AMR AF: 0.476

Gnomad ASJ AF: 0.661

Gnomad EAS AF: 0.310

Gnomad SAS AF: 0.679

Gnomad FIN AF: 0.502

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.555

Gnomad OTH AF: 0.601

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

GnomAD4 genome AF: 0.611 AC: 92841 AN: 152042 Hom.: 29792 Cov.: 32 AF XY: 0.604 AC XY: 44883 AN XY: 74332

African (AFR) AF: 0.805 AC: 33367 AN: 41428

American (AMR) AF: 0.476 AC: 7265 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.661 AC: 2295 AN: 3470

East Asian (EAS) AF: 0.310 AC: 1605 AN: 5178

South Asian (SAS) AF: 0.679 AC: 3275 AN: 4822

European-Finnish (FIN) AF: 0.502 AC: 5312 AN: 10574

Middle Eastern (MID) AF: 0.660 AC: 194 AN: 294

European-Non Finnish (NFE) AF: 0.555 AC: 37715 AN: 67978

Other (OTH) AF: 0.603 AC: 1272 AN: 2110

Alfa AF: 0.569 Hom.: 14740

Bravo AF: 0.612

Asia WGS AF: 0.514 AC: 1787 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	0.47
DANN	Benign	0.72
PhyloP100		-0.26
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1035089;

hg19: chr16-11048350;