chr16-83748314-T-C

Variant names:

• chr16-83748314-T-C
• rs889490
• NM_001257.5:c.1681+64T>C

Variant summary

Our verdict is Benign. The variant received -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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CDH13	NM_001257.5	c.1681+64T>C		intron_variant	Intron 11 of 13	ENST00000567109.6	NP_001248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH13	ENST00000567109.6	c.1681+64T>C		intron_variant	Intron 11 of 13	1	NM_001257.5	ENSP00000479395.1

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 AC: 11358 AN: 29690

Gnomad4 AMR exome AF: 0.0630 AC: 2133 AN: 33832

Gnomad4 ASJ exome AF: 0.145 AC: 3075 AN: 21232

Gnomad4 EAS exome AF: 0.0275 AC: 1056 AN: 38440

Gnomad4 SAS exome AF: 0.156 AC: 10577 AN: 67720

Gnomad4 FIN exome AF: 0.102 AC: 5088 AN: 49754

Gnomad4 NFE exome AF: 0.0837 AC: 84759 AN: 1012182

Gnomad4 Remaining exome AF: 0.104 AC: 5680 AN: 54544

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 AC: 0.368388 AN: 0.368388

Gnomad4 AMR AF: 0.0927 AC: 0.0926797 AN: 0.0926797

Gnomad4 ASJ AF: 0.149 AC: 0.149366 AN: 0.149366

Gnomad4 EAS AF: 0.0118 AC: 0.0117624 AN: 0.0117624

Gnomad4 SAS AF: 0.153 AC: 0.1534 AN: 0.1534

Gnomad4 FIN AF: 0.106 AC: 0.106046 AN: 0.106046

Gnomad4 NFE AF: 0.0867 AC: 0.0867315 AN: 0.0867315

Gnomad4 OTH AF: 0.137 AC: 0.137181 AN: 0.137181

Alfa AF: 0.111 Hom.: 1646

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

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs889490; hg19: chr16-83781919;