chr16-83780017-C-T

Variant names:

• chr16-83780017-C-T
• rs151311546
• NM_001257.5:c.1731C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Moderate BP6 BP7 BS2

The NM_001257.5(CDH13):​c.1731C>T​(p.Asp577Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000758 in 1,613,952 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00063 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00077 (2 hom.)
• Consequence: CDH13 NM_001257.5 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.0370
• Publications: 2 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]

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant 16-83780017-C-T is Benign according to our data. Variant chr16-83780017-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3042892.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-0.037 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 2 gene

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.1731C>T	p.Asp577Asp	synonymous	Exon 12 of 14	NP_001248.1	P55290-1
	CDH13	NM_001220488.2		c.1872C>T	p.Asp624Asp	synonymous	Exon 13 of 15	NP_001207417.1	P55290-4
	CDH13	NM_001220489.2		c.1614C>T	p.Asp538Asp	synonymous	Exon 11 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.1731C>T	p.Asp577Asp	synonymous	Exon 12 of 14	ENSP00000479395.1	P55290-1
	CDH13	ENST00000268613.14	TSL:2	c.1872C>T	p.Asp624Asp	synonymous	Exon 13 of 15	ENSP00000268613.10	P55290-4
	CDH13	ENST00000428848.7	TSL:2	c.1614C>T	p.Asp538Asp	synonymous	Exon 11 of 13	ENSP00000394557.3	P55290-5

Frequencies

GnomAD3 genomes AF: 0.000631 AC: 96 AN: 152194 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000290

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.000289

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00101

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.000686 AC: 171 AN: 249208 AF XY: 0.000762

Gnomad AFR exome AF: 0.000258

Gnomad AMR exome AF: 0.000579

Gnomad ASJ exome AF: 0.000398

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000464

Gnomad NFE exome AF: 0.000956

Gnomad OTH exome AF: 0.00198

GnomAD4 exome AF: 0.000772 AC: 1128 AN: 1461640 Hom.: 2 Cov.: 31 AF XY: 0.000787 AC XY: 572 AN XY: 727098

African (AFR) AF: 0.000329 AC: 11 AN: 33478

American (AMR) AF: 0.000514 AC: 23 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.000153 AC: 4 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000823 AC: 71 AN: 86250

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53402

Middle Eastern (MID) AF: 0.00641 AC: 37 AN: 5768

European-Non Finnish (NFE) AF: 0.000818 AC: 909 AN: 1111818

Other (OTH) AF: 0.00119 AC: 72 AN: 60372

GnomAD4 genome AF: 0.000630 AC: 96 AN: 152312 Hom.: 0 Cov.: 33 AF XY: 0.000537 AC XY: 40 AN XY: 74476

African (AFR) AF: 0.000289 AC: 12 AN: 41566

American (AMR) AF: 0.000457 AC: 7 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.000289 AC: 1 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00101 AC: 69 AN: 68018

Other (OTH) AF: 0.00142 AC: 3 AN: 2116

Alfa AF: 0.00101 Hom.: 0

Bravo AF: 0.000680

EpiCase AF: 0.00125

EpiControl AF: 0.00130

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	CDH13-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	9.7
DANN	Benign	0.82
PhyloP100		-0.037
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs151311546; hg19: chr16-83813622; COSMIC: COSV99231220;