chr16-83779817-C-T

Position:

• chr16-83779817-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001257.5(CDH13):​c.1682-151C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0297 in 582,746 control chromosomes in the GnomAD database, including 369 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.027 (93 hom., cov: 32)
  • Exomes 𝑓: 0.031 (276 hom.)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.07

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]

HSBP1 (HGNC:5203): (heat shock factor binding protein 1) The heat-shock response is elicited by exposure of cells to thermal and chemical stress and through the activation of HSFs (heat shock factors) results in the elevated expression of heat-shock induced genes. Heat shock factor binding protein 1 (HSBP1), is a 76-amino-acid protein that binds to heat shock factor 1(HSF1), which is a transcription factor involved in the HS response. During HS response, HSF1 undergoes conformational transition from an inert non-DNA-binding monomer to active functional trimers. HSBP1 is nuclear-localized and interacts with the active trimeric state of HSF1 to negatively regulate HSF1 DNA-binding activity. Overexpression of HSBP1 in mammalian cells represses the transactivation activity of HSF1. When overexpressed in C.elegans HSBP1 has severe effects on survival of the animals after thermal and chemical stress consistent with a role of HSBP1 as a negative regulator of heat shock response. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 16-83779817-C-T is Benign according to our data. Variant chr16-83779817-C-T is described in ClinVar as [Benign]. Clinvar id is 1237494.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0269 (4095/152248) while in subpopulation NFE AF= 0.0381 (2593/68016). AF 95% confidence interval is 0.0369. There are 93 homozygotes in gnomad4. There are 2041 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 93 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDH13	NM_001257.5	c.1682-151C>T		intron_variant		ENST00000567109.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH13	ENST00000567109.6	c.1682-151C>T		intron_variant		1	NM_001257.5	P1

Frequencies

GnomAD3 genomes AF: 0.0269 AC: 4094 AN: 152130 Hom.: 93 Cov.: 32

Gnomad AFR AF: 0.00679

Gnomad AMI AF: 0.0989

Gnomad AMR AF: 0.0225

Gnomad ASJ AF: 0.00605

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0147

Gnomad FIN AF: 0.0603

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0381

Gnomad OTH AF: 0.0225

GnomAD4 exome AF: 0.0307 AC: 13209 AN: 430498 Hom.: 276 AF XY: 0.0301 AC XY: 6731 AN XY: 223958

Gnomad4 AFR exome AF: 0.00707

Gnomad4 AMR exome AF: 0.0188

Gnomad4 ASJ exome AF: 0.00775

Gnomad4 EAS exome AF: 0.000197

Gnomad4 SAS exome AF: 0.0146

Gnomad4 FIN exome AF: 0.0590

Gnomad4 NFE exome AF: 0.0364

Gnomad4 OTH exome AF: 0.0297

GnomAD4 genome AF: 0.0269 AC: 4095 AN: 152248 Hom.: 93 Cov.: 32 AF XY: 0.0274 AC XY: 2041 AN XY: 74446

Gnomad4 AFR AF: 0.00677

Gnomad4 AMR AF: 0.0225

Gnomad4 ASJ AF: 0.00605

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0151

Gnomad4 FIN AF: 0.0603

Gnomad4 NFE AF: 0.0381

Gnomad4 OTH AF: 0.0222

Alfa AF: 0.0109 Hom.: 4

Bravo AF: 0.0231

Asia WGS AF: 0.0110 AC: 37 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 18, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.7
DANN	Benign	0.65

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

Publications

LitVar

Other links and lift over

dbSNP: rs72802876; hg19: chr16-83813422;