16-83678282-C-T

Variant names:

• chr16-83678282-C-T
• rs34697339
• NM_001257.5:c.1359C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001257.5(CDH13):​c.1359C>T​(p.Asp453Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0396 in 1,613,856 control chromosomes in the GnomAD database, including 1,819 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.063 (463 hom., cov: 32)
  • Exomes 𝑓: 0.037 (1356 hom.)
• Consequence: CDH13 NM_001257.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.95
• Publications: 3 publications found

Genes affected

CDH13 (HGNC:1753): (cadherin 13) This gene encodes a member of the cadherin superfamily. The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety, rather than by a transmembrane domain. The protein lacks the cytoplasmic domain characteristic of other cadherins, and so is not thought to be a cell-cell adhesion glycoprotein. This protein acts as a negative regulator of axon growth during neural differentiation. It also protects vascular endothelial cells from apoptosis due to oxidative stress, and is associated with resistance to atherosclerosis. The gene is hypermethylated in many types of cancer. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, May 2011]

ENSG00000261103 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 16-83678282-C-T is Benign according to our data. Variant chr16-83678282-C-T is described in ClinVar as Benign. ClinVar VariationId is 257643.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.95 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.126 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001257.5. 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
	CDH13	NM_001257.5	MANE Select	c.1359C>T	p.Asp453Asp	synonymous	Exon 10 of 14	NP_001248.1	P55290-1
	CDH13	NM_001220488.2		c.1500C>T	p.Asp500Asp	synonymous	Exon 11 of 15	NP_001207417.1	P55290-4
	CDH13	NM_001220489.2		c.1242C>T	p.Asp414Asp	synonymous	Exon 9 of 13	NP_001207418.1	P55290-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH13	ENST00000567109.6	TSL:1 MANE Select	c.1359C>T	p.Asp453Asp	synonymous	Exon 10 of 14	ENSP00000479395.1	P55290-1
	CDH13	ENST00000268613.14	TSL:2	c.1500C>T	p.Asp500Asp	synonymous	Exon 11 of 15	ENSP00000268613.10	P55290-4
	CDH13	ENST00000428848.7	TSL:2	c.1242C>T	p.Asp414Asp	synonymous	Exon 9 of 13	ENSP00000394557.3	P55290-5

Frequencies

GnomAD3 genomes AF: 0.0631 AC: 9592 AN: 152066 Hom.: 461 Cov.: 32

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.0308

Gnomad AMR AF: 0.0375

Gnomad ASJ AF: 0.0412

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.0475

Gnomad FIN AF: 0.0873

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0329

Gnomad OTH AF: 0.0475

GnomAD2 exomes AF: 0.0429 AC: 10684 AN: 249166 AF XY: 0.0423

Gnomad AFR exome AF: 0.133

Gnomad AMR exome AF: 0.0233

Gnomad ASJ exome AF: 0.0434

Gnomad EAS exome AF: 0.00223

Gnomad FIN exome AF: 0.0829

Gnomad NFE exome AF: 0.0339

Gnomad OTH exome AF: 0.0357

GnomAD4 exome AF: 0.0371 AC: 54242 AN: 1461672 Hom.: 1356 Cov.: 32 AF XY: 0.0371 AC XY: 26993 AN XY: 727124

African (AFR) AF: 0.135 AC: 4532 AN: 33480

American (AMR) AF: 0.0255 AC: 1140 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0422 AC: 1103 AN: 26134

East Asian (EAS) AF: 0.00128 AC: 51 AN: 39698

South Asian (SAS) AF: 0.0472 AC: 4075 AN: 86256

European-Finnish (FIN) AF: 0.0783 AC: 4182 AN: 53402

Middle Eastern (MID) AF: 0.0326 AC: 188 AN: 5768

European-Non Finnish (NFE) AF: 0.0330 AC: 36647 AN: 1111836

Other (OTH) AF: 0.0385 AC: 2324 AN: 60374

GnomAD4 genome AF: 0.0632 AC: 9611 AN: 152184 Hom.: 463 Cov.: 32 AF XY: 0.0652 AC XY: 4853 AN XY: 74408

African (AFR) AF: 0.129 AC: 5346 AN: 41494

American (AMR) AF: 0.0375 AC: 573 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0412 AC: 143 AN: 3470

East Asian (EAS) AF: 0.00232 AC: 12 AN: 5172

South Asian (SAS) AF: 0.0479 AC: 231 AN: 4820

European-Finnish (FIN) AF: 0.0873 AC: 926 AN: 10602

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0329 AC: 2238 AN: 68024

Other (OTH) AF: 0.0470 AC: 99 AN: 2108

Alfa AF: 0.0416 Hom.: 168

Bravo AF: 0.0622

Asia WGS AF: 0.0370 AC: 128 AN: 3478

EpiCase AF: 0.0320

EpiControl AF: 0.0354

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.096
DANN	Benign	0.55
PhyloP100		-2.0
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: rs34697339; hg19: chr16-83711887; COSMIC: COSV108043523;