rs918684

Variant names:

• chr16-83780471-T-A
• rs918684
• NM_001257.5:c.1915+270T>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001257.5(CDH13):​c.1915+270T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 152,172 control chromosomes in the GnomAD database, including 4,264 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.21 (4264 hom., cov: 32)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0370
• Publications: 1 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 16-83780471-T-A is Benign according to our data. Variant chr16-83780471-T-A is described in ClinVar as Benign. ClinVar VariationId is 1239122.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.582 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.1915+270T>A		intron	N/A	NP_001248.1	P55290-1
	CDH13	NM_001220488.2		c.2056+270T>A		intron	N/A	NP_001207417.1	P55290-4
	CDH13	NM_001220489.2		c.1798+270T>A		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.1915+270T>A		intron	N/A	ENSP00000479395.1	P55290-1
	CDH13	ENST00000268613.14	TSL:2	c.2056+270T>A		intron	N/A	ENSP00000268613.10	P55290-4
	CDH13	ENST00000428848.7	TSL:2	c.1798+270T>A		intron	N/A	ENSP00000394557.3	P55290-5

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32645 AN: 152054 Hom.: 4264 Cov.: 32

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.600

Gnomad SAS AF: 0.342

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.237

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

GnomAD4 genome AF: 0.215 AC: 32671 AN: 152172 Hom.: 4264 Cov.: 32 AF XY: 0.223 AC XY: 16610 AN XY: 74400

African (AFR) AF: 0.153 AC: 6364 AN: 41540

American (AMR) AF: 0.339 AC: 5182 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 828 AN: 3472

East Asian (EAS) AF: 0.599 AC: 3097 AN: 5166

South Asian (SAS) AF: 0.340 AC: 1637 AN: 4818

European-Finnish (FIN) AF: 0.231 AC: 2446 AN: 10580

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.183 AC: 12421 AN: 68002

Other (OTH) AF: 0.237 AC: 500 AN: 2110

Alfa AF: 0.195 Hom.: 408

Bravo AF: 0.221

Asia WGS AF: 0.443 AC: 1541 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.2
DANN	Benign	0.39
PhyloP100		-0.037
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: rs918684; hg19: chr16-83814076;