chr16-10969154-C-T

Variant names:

• chr16-10969154-C-T
• rs2302558
• NM_015226.3:c.344-7C>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.344-7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 1,594,830 control chromosomes in the GnomAD database, including 19,051 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.21 (4478 hom., cov: 31)
  • Exomes 𝑓: 0.13 (14573 hom.)
• Consequence: CLEC16A NM_015226.3 splice_region, intron
• Scores: Splicing: ADA: 0.00002818
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.138
• Publications: 15 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=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.4 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.344-7C>T		splice_region intron	N/A	NP_056041.1
	CLEC16A	NM_001410905.1		c.344-7C>T		splice_region intron	N/A	NP_001397834.1
	CLEC16A	NM_001243403.2		c.344-7C>T		splice_region 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.344-7C>T		splice_region intron	N/A	ENSP00000387122.1
	CLEC16A	ENST00000409552.4	TSL:1	c.344-7C>T		splice_region intron	N/A	ENSP00000386495.3
	CLEC16A	ENST00000703130.1		c.344-7C>T		splice_region intron	N/A	ENSP00000515187.1

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31828 AN: 151694 Hom.: 4460 Cov.: 31

Gnomad AFR AF: 0.405

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.130

Gnomad OTH AF: 0.198

GnomAD2 exomes AF: 0.144 AC: 34216 AN: 237476 AF XY: 0.143

Gnomad AFR exome AF: 0.407

Gnomad AMR exome AF: 0.104

Gnomad ASJ exome AF: 0.161

Gnomad EAS exome AF: 0.109

Gnomad FIN exome AF: 0.142

Gnomad NFE exome AF: 0.125

Gnomad OTH exome AF: 0.136

GnomAD4 exome AF: 0.133 AC: 192522 AN: 1443018 Hom.: 14573 Cov.: 30 AF XY: 0.134 AC XY: 96158 AN XY: 718350

African (AFR) AF: 0.411 AC: 13189 AN: 32058

American (AMR) AF: 0.107 AC: 4396 AN: 41122

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 4184 AN: 25784

East Asian (EAS) AF: 0.0824 AC: 3254 AN: 39478

South Asian (SAS) AF: 0.149 AC: 12515 AN: 84254

European-Finnish (FIN) AF: 0.141 AC: 7445 AN: 52750

Middle Eastern (MID) AF: 0.181 AC: 1000 AN: 5540

European-Non Finnish (NFE) AF: 0.125 AC: 138028 AN: 1102380

Other (OTH) AF: 0.143 AC: 8511 AN: 59652

GnomAD4 genome AF: 0.210 AC: 31893 AN: 151812 Hom.: 4478 Cov.: 31 AF XY: 0.207 AC XY: 15382 AN XY: 74202

African (AFR) AF: 0.405 AC: 16740 AN: 41328

American (AMR) AF: 0.147 AC: 2249 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.173 AC: 600 AN: 3466

East Asian (EAS) AF: 0.111 AC: 573 AN: 5162

South Asian (SAS) AF: 0.145 AC: 697 AN: 4812

European-Finnish (FIN) AF: 0.153 AC: 1609 AN: 10538

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

European-Non Finnish (NFE) AF: 0.130 AC: 8844 AN: 67942

Other (OTH) AF: 0.200 AC: 423 AN: 2110

Alfa AF: 0.153 Hom.: 4288

Bravo AF: 0.218

Asia WGS AF: 0.146 AC: 505 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	5.6
DANN	Benign	0.55
PhyloP100		0.14
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000028
dbscSNV1_RF	Benign	0.0
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: rs2302558; hg19: chr16-11063011; COSMIC: COSV68500413; COSMIC: COSV68500413;