16-11178313-C-T

Variant names:

• chr16-11178313-C-T
• rs72650661
• NM_015226.3:c.2807-22C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_015226.3(CLEC16A):​c.2807-22C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0151 in 1,583,626 control chromosomes in the GnomAD database, including 215 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 0.012 (22 hom., cov: 33)
  • Exomes 𝑓: 0.015 (193 hom.)
• Consequence: CLEC16A NM_015226.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.69
• Publications: 2 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=-0.92).
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0115 (1753/152298) while in subpopulation AMR AF = 0.0205 (313/15302). AF 95% confidence interval is 0.0186. There are 22 homozygotes in GnomAd4. There are 825 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 22 Unknown gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLEC16A	NM_015226.3	c.2807-22C>T		intron_variant	Intron 23 of 23	ENST00000409790.6	NP_056041.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLEC16A	ENST00000409790.6	c.2807-22C>T		intron_variant	Intron 23 of 23	5	NM_015226.3	ENSP00000387122.1
CLEC16A	ENST00000703130.1	c.2801-22C>T		intron_variant	Intron 22 of 22			ENSP00000515187.1
CLEC16A	ENST00000261657.5	c.*48-22C>T		intron_variant	Intron 4 of 4	4		ENSP00000261657.5

Frequencies

GnomAD3 genomes AF: 0.0115 AC: 1753 AN: 152180 Hom.: 22 Cov.: 33

Gnomad AFR AF: 0.00331

Gnomad AMI AF: 0.0570

Gnomad AMR AF: 0.0205

Gnomad ASJ AF: 0.00980

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00538

Gnomad FIN AF: 0.00151

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0168

Gnomad OTH AF: 0.0129

GnomAD2 exomes AF: 0.0105 AC: 2485 AN: 237350 AF XY: 0.0108

Gnomad AFR exome AF: 0.00253

Gnomad AMR exome AF: 0.00883

Gnomad ASJ exome AF: 0.00956

Gnomad EAS exome AF: 0.0000558

Gnomad FIN exome AF: 0.00254

Gnomad NFE exome AF: 0.0160

Gnomad OTH exome AF: 0.0121

GnomAD4 exome AF: 0.0155 AC: 22164 AN: 1431328 Hom.: 193 Cov.: 29 AF XY: 0.0152 AC XY: 10728 AN XY: 707932

African (AFR) AF: 0.00206 AC: 68 AN: 33054

American (AMR) AF: 0.00892 AC: 391 AN: 43832

Ashkenazi Jewish (ASJ) AF: 0.00972 AC: 241 AN: 24806

East Asian (EAS) AF: 0.000102 AC: 4 AN: 39232

South Asian (SAS) AF: 0.00824 AC: 685 AN: 83082

European-Finnish (FIN) AF: 0.00262 AC: 136 AN: 51970

Middle Eastern (MID) AF: 0.00707 AC: 40 AN: 5654

European-Non Finnish (NFE) AF: 0.0180 AC: 19672 AN: 1090584

Other (OTH) AF: 0.0157 AC: 927 AN: 59114

GnomAD4 genome AF: 0.0115 AC: 1753 AN: 152298 Hom.: 22 Cov.: 33 AF XY: 0.0111 AC XY: 825 AN XY: 74478

African (AFR) AF: 0.00330 AC: 137 AN: 41568

American (AMR) AF: 0.0205 AC: 313 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00980 AC: 34 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00539 AC: 26 AN: 4828

European-Finnish (FIN) AF: 0.00151 AC: 16 AN: 10614

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0168 AC: 1145 AN: 68016

Other (OTH) AF: 0.0128 AC: 27 AN: 2110

Alfa AF: 0.00773 Hom.: 0

Bravo AF: 0.0119

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.9
DANN	Benign	0.61
PhyloP100		1.7
Mutation Taster		=100/0	polymorphism

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: rs72650661; hg19: chr16-11272170; COSMIC: COSV55490966;