16-10969154-C-T

Position:

• chr16-10969154-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015226.3(CLEC16A):​c.344-7C>T variant causes a splice region, splice polypyrimidine tract, 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, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00002818
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.138

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLEC16A	NM_015226.3	c.344-7C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000409790.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLEC16A	ENST00000409790.6	c.344-7C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5	NM_015226.3	A1
CLEC16A	ENST00000409552.4	c.344-7C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1
CLEC16A	ENST00000703130.1	c.344-7C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant				P4

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

GnomAD3 exomes AF: 0.144 AC: 34216 AN: 237476 Hom.: 3067 AF XY: 0.143 AC XY: 18421 AN XY: 129180

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 SAS exome AF: 0.145

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

Gnomad4 AFR exome AF: 0.411

Gnomad4 AMR exome AF: 0.107

Gnomad4 ASJ exome AF: 0.162

Gnomad4 EAS exome AF: 0.0824

Gnomad4 SAS exome AF: 0.149

Gnomad4 FIN exome AF: 0.141

Gnomad4 NFE exome AF: 0.125

Gnomad4 OTH exome AF: 0.143

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

Gnomad4 AFR AF: 0.405

Gnomad4 AMR AF: 0.147

Gnomad4 ASJ AF: 0.173

Gnomad4 EAS AF: 0.111

Gnomad4 SAS AF: 0.145

Gnomad4 FIN AF: 0.153

Gnomad4 NFE AF: 0.130

Gnomad4 OTH AF: 0.200

Alfa AF: 0.147 Hom.: 3176

Bravo AF: 0.218

Asia WGS AF: 0.146 AC: 505 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	5.6
DANN	Benign	0.55
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs2302558; hg19: chr16-11063011; COSMIC: COSV68500413; COSMIC: COSV68500413;