16-11047464-T-C

Variant names:

• chr16-11047464-T-C
• rs16957976
• NM_015226.3:c.1866+122T>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.1866+122T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 522,824 control chromosomes in the GnomAD database, including 3,313 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 0.12 (1139 hom., cov: 32)
  • Exomes 𝑓: 0.10 (2174 hom.)
• Consequence: CLEC16A NM_015226.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.337
• Publications: 13 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.157 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.1866+122T>C		intron	N/A	NP_056041.1
	CLEC16A	NM_001410905.1		c.1860+122T>C		intron	N/A	NP_001397834.1
	CLEC16A	NM_001243403.2		c.1812+122T>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.1866+122T>C		intron	N/A	ENSP00000387122.1
	CLEC16A	ENST00000409552.4	TSL:1	c.1812+122T>C		intron	N/A	ENSP00000386495.3
	CLEC16A	ENST00000463896.5	TSL:2	n.3038T>C		non_coding_transcript_exon	Exon 5 of 5

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18217 AN: 152022 Hom.: 1136 Cov.: 32

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.115

Gnomad ASJ AF: 0.0972

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.0481

Gnomad FIN AF: 0.0911

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.133

GnomAD4 exome AF: 0.103 AC: 38281 AN: 370684 Hom.: 2174 Cov.: 6 AF XY: 0.102 AC XY: 19363 AN XY: 190624

African (AFR) AF: 0.157 AC: 1429 AN: 9082

American (AMR) AF: 0.116 AC: 990 AN: 8504

Ashkenazi Jewish (ASJ) AF: 0.0916 AC: 971 AN: 10598

East Asian (EAS) AF: 0.126 AC: 2954 AN: 23444

South Asian (SAS) AF: 0.0440 AC: 738 AN: 16758

European-Finnish (FIN) AF: 0.0942 AC: 2900 AN: 30778

Middle Eastern (MID) AF: 0.111 AC: 179 AN: 1612

European-Non Finnish (NFE) AF: 0.103 AC: 25784 AN: 249130

Other (OTH) AF: 0.112 AC: 2336 AN: 20778

GnomAD4 genome AF: 0.120 AC: 18234 AN: 152140 Hom.: 1139 Cov.: 32 AF XY: 0.119 AC XY: 8814 AN XY: 74374

African (AFR) AF: 0.160 AC: 6628 AN: 41494

American (AMR) AF: 0.115 AC: 1752 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0972 AC: 337 AN: 3468

East Asian (EAS) AF: 0.115 AC: 597 AN: 5170

South Asian (SAS) AF: 0.0481 AC: 232 AN: 4822

European-Finnish (FIN) AF: 0.0911 AC: 965 AN: 10592

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.107 AC: 7254 AN: 67984

Other (OTH) AF: 0.133 AC: 281 AN: 2112

Alfa AF: 0.111 Hom.: 1653

Bravo AF: 0.125

Asia WGS AF: 0.100 AC: 346 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.7
DANN	Benign	0.85
PhyloP100		-0.34
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: rs16957976; hg19: chr16-11141321;