NM_001257.5:c.1539-109T>C

Variant names:

• chr16-83747999-T-C
• rs16961631
• NM_001257.5:c.1539-109T>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.1539-109T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 1,152,732 control chromosomes in the GnomAD database, including 79,216 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.36 (10035 hom., cov: 30)
  • Exomes 𝑓: 0.37 (69181 hom.)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0220
• Publications: 9 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]

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=-0.85).
• BP6: Variant 16-83747999-T-C is Benign according to our data. Variant chr16-83747999-T-C is described in ClinVar as Benign. ClinVar VariationId is 1241198.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

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.1539-109T>C		intron	N/A	NP_001248.1	P55290-1
	CDH13	NM_001220488.2		c.1680-109T>C		intron	N/A	NP_001207417.1	P55290-4
	CDH13	NM_001220489.2		c.1422-109T>C		intron	N/A	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.1539-109T>C		intron	N/A	ENSP00000479395.1	P55290-1
	CDH13	ENST00000268613.14	TSL:2	c.1680-109T>C		intron	N/A	ENSP00000268613.10	P55290-4
	CDH13	ENST00000428848.7	TSL:2	c.1422-109T>C		intron	N/A	ENSP00000394557.3	P55290-5

Frequencies

GnomAD3 genomes AF: 0.363 AC: 55046 AN: 151692 Hom.: 10030 Cov.: 30

Gnomad AFR AF: 0.329

Gnomad AMI AF: 0.375

Gnomad AMR AF: 0.383

Gnomad ASJ AF: 0.330

Gnomad EAS AF: 0.419

Gnomad SAS AF: 0.368

Gnomad FIN AF: 0.411

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.368

Gnomad OTH AF: 0.362

GnomAD4 exome AF: 0.368 AC: 368375 AN: 1000922 Hom.: 69181 AF XY: 0.368 AC XY: 188072 AN XY: 511602

African (AFR) AF: 0.337 AC: 8143 AN: 24176

American (AMR) AF: 0.395 AC: 15316 AN: 38728

Ashkenazi Jewish (ASJ) AF: 0.326 AC: 6750 AN: 20722

East Asian (EAS) AF: 0.440 AC: 16403 AN: 37308

South Asian (SAS) AF: 0.357 AC: 24846 AN: 69630

European-Finnish (FIN) AF: 0.401 AC: 19513 AN: 48618

Middle Eastern (MID) AF: 0.428 AC: 1983 AN: 4638

European-Non Finnish (NFE) AF: 0.364 AC: 259106 AN: 712442

Other (OTH) AF: 0.365 AC: 16315 AN: 44660

GnomAD4 genome AF: 0.363 AC: 55086 AN: 151810 Hom.: 10035 Cov.: 30 AF XY: 0.363 AC XY: 26905 AN XY: 74170

African (AFR) AF: 0.329 AC: 13599 AN: 41378

American (AMR) AF: 0.383 AC: 5840 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.330 AC: 1145 AN: 3468

East Asian (EAS) AF: 0.421 AC: 2171 AN: 5162

South Asian (SAS) AF: 0.366 AC: 1760 AN: 4806

European-Finnish (FIN) AF: 0.411 AC: 4327 AN: 10532

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.368 AC: 25023 AN: 67914

Other (OTH) AF: 0.363 AC: 763 AN: 2102

Alfa AF: 0.362 Hom.: 4462

Bravo AF: 0.362

Asia WGS AF: 0.419 AC: 1462 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.2
DANN	Benign	0.53
PhyloP100		0.022
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

Other links and lift over

dbSNP: rs16961631; hg19: chr16-83781604; COSMIC: COSV51824858;