chr16-83779689-T-C

Position:

• chr16-83779689-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001257.5(CDH13):​c.1682-279T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 151,634 control chromosomes in the GnomAD database, including 5,511 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.25 (5511 hom., cov: 31)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0470

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BP6: Variant 16-83779689-T-C is Benign according to our data. Variant chr16-83779689-T-C is described in ClinVar as [Benign]. Clinvar id is 1296159.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDH13	NM_001257.5	c.1682-279T>C		intron_variant		ENST00000567109.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH13	ENST00000567109.6	c.1682-279T>C		intron_variant		1	NM_001257.5	P1

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38341 AN: 151514 Hom.: 5503 Cov.: 31

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.367

Gnomad ASJ AF: 0.245

Gnomad EAS AF: 0.619

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.293

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.221

Gnomad OTH AF: 0.265

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.253 AC: 38378 AN: 151634 Hom.: 5511 Cov.: 31 AF XY: 0.261 AC XY: 19363 AN XY: 74054

Gnomad4 AFR AF: 0.197

Gnomad4 AMR AF: 0.368

Gnomad4 ASJ AF: 0.245

Gnomad4 EAS AF: 0.619

Gnomad4 SAS AF: 0.354

Gnomad4 FIN AF: 0.293

Gnomad4 NFE AF: 0.221

Gnomad4 OTH AF: 0.265

Alfa AF: 0.229 Hom.: 3232

Bravo AF: 0.257

Asia WGS AF: 0.465 AC: 1618 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 18, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	2.0
DANN	Benign	0.25

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: rs1981860; hg19: chr16-83813294;