16-83745465-A-G

Variant names:

• chr16-83745465-A-G
• rs3784990
• NM_001257.5:c.1539-2643A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001257.5(CDH13):​c.1539-2643A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.701 in 152,036 control chromosomes in the GnomAD database, including 37,956 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.70 (37956 hom., cov: 32)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0990
• Publications: 5 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.961 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH13	NM_001257.5	MANE Select	c.1539-2643A>G		intron	N/A	NP_001248.1
	CEDORA	NR_199711.1		n.1262T>C		non_coding_transcript_exon	Exon 2 of 2
	CDH13	NM_001220488.2		c.1680-2643A>G		intron	N/A	NP_001207417.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH13	ENST00000567109.6	TSL:1 MANE Select	c.1539-2643A>G		intron	N/A	ENSP00000479395.1
	CEDORA	ENST00000670287.1		n.1262T>C		non_coding_transcript_exon	Exon 2 of 2
	CDH13	ENST00000268613.14	TSL:2	c.1680-2643A>G		intron	N/A	ENSP00000268613.10

Frequencies

GnomAD3 genomes AF: 0.701 AC: 106447 AN: 151920 Hom.: 37938 Cov.: 32

Gnomad AFR AF: 0.608

Gnomad AMI AF: 0.673

Gnomad AMR AF: 0.785

Gnomad ASJ AF: 0.641

Gnomad EAS AF: 0.984

Gnomad SAS AF: 0.779

Gnomad FIN AF: 0.800

Gnomad MID AF: 0.753

Gnomad NFE AF: 0.698

Gnomad OTH AF: 0.710

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

GnomAD4 genome AF: 0.701 AC: 106513 AN: 152036 Hom.: 37956 Cov.: 32 AF XY: 0.711 AC XY: 52844 AN XY: 74326

African (AFR) AF: 0.608 AC: 25202 AN: 41454

American (AMR) AF: 0.785 AC: 11998 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.641 AC: 2221 AN: 3466

East Asian (EAS) AF: 0.984 AC: 5072 AN: 5154

South Asian (SAS) AF: 0.779 AC: 3752 AN: 4818

European-Finnish (FIN) AF: 0.800 AC: 8457 AN: 10572

Middle Eastern (MID) AF: 0.745 AC: 219 AN: 294

European-Non Finnish (NFE) AF: 0.698 AC: 47473 AN: 67976

Other (OTH) AF: 0.713 AC: 1507 AN: 2114

Alfa AF: 0.702 Hom.: 83361

Bravo AF: 0.697

Asia WGS AF: 0.872 AC: 3032 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.88
DANN	Benign	0.29
PhyloP100		-0.099
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: rs3784990; hg19: chr16-83779070; COSMIC: COSV51828840;