16-83748314-T-C

Position:

• chr16-83748314-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001257.5(CDH13):​c.1681+64T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 1,464,850 control chromosomes in the GnomAD database, including 11,181 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (3353 hom., cov: 32)
  • Exomes 𝑓: 0.095 (7828 hom.)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.106

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]

CEDORA (HGNC:56653): (CDH13 antisense oligodendrocyte and neuron associated lncRNA)

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=-0.83).
• BP6: Variant 16-83748314-T-C is Benign according to our data. Variant chr16-83748314-T-C is described in ClinVar as [Benign]. Clinvar id is 1252548.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.363 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDH13	NM_001257.5	c.1681+64T>C		intron_variant		ENST00000567109.6
CEDORA	XR_007065143.1	n.142-12396A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH13	ENST00000567109.6	c.1681+64T>C		intron_variant		1	NM_001257.5	P1
CEDORA	ENST00000570056.2	n.142-19315A>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25464 AN: 152102 Hom.: 3337 Cov.: 32

Gnomad AFR AF: 0.368

Gnomad AMI AF: 0.172

Gnomad AMR AF: 0.0929

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.0117

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0867

Gnomad OTH AF: 0.139

GnomAD4 exome AF: 0.0948 AC: 124454 AN: 1312630 Hom.: 7828 AF XY: 0.0962 AC XY: 62157 AN XY: 646348

Gnomad4 AFR exome AF: 0.383

Gnomad4 AMR exome AF: 0.0630

Gnomad4 ASJ exome AF: 0.145

Gnomad4 EAS exome AF: 0.0275

Gnomad4 SAS exome AF: 0.156

Gnomad4 FIN exome AF: 0.102

Gnomad4 NFE exome AF: 0.0837

Gnomad4 OTH exome AF: 0.104

GnomAD4 genome AF: 0.168 AC: 25519 AN: 152220 Hom.: 3353 Cov.: 32 AF XY: 0.167 AC XY: 12431 AN XY: 74430

Gnomad4 AFR AF: 0.368

Gnomad4 AMR AF: 0.0927

Gnomad4 ASJ AF: 0.149

Gnomad4 EAS AF: 0.0118

Gnomad4 SAS AF: 0.153

Gnomad4 FIN AF: 0.106

Gnomad4 NFE AF: 0.0867

Gnomad4 OTH AF: 0.137

Alfa AF: 0.0997 Hom.: 886

Bravo AF: 0.172

Asia WGS AF: 0.0930 AC: 324 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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.7
DANN	Benign	0.79

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: rs889490; hg19: chr16-83781919;