rs723919

Variant names:

• chr16-83308629-G-A
• rs723919
• NM_001257.5:c.637-36233G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-83308629-G-A
• chr16-83308629-G-C

Variant summary

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

The NM_001257.5(CDH13):​c.637-36233G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.44 in 152,104 control chromosomes in the GnomAD database, including 15,396 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 0.44 (15396 hom., cov: 33)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0810
• 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.508 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.637-36233G>A		intron	N/A	NP_001248.1	P55290-1
	CDH13	NM_001220488.2		c.778-36233G>A		intron	N/A	NP_001207417.1	P55290-4
	CDH13	NM_001220489.2		c.520-36233G>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.637-36233G>A		intron	N/A	ENSP00000479395.1	P55290-1
	CDH13	ENST00000268613.14	TSL:2	c.778-36233G>A		intron	N/A	ENSP00000268613.10	P55290-4
	CDH13	ENST00000428848.7	TSL:2	c.520-36233G>A		intron	N/A	ENSP00000394557.3	P55290-5

Frequencies

GnomAD3 genomes AF: 0.440 AC: 66908 AN: 151984 Hom.: 15389 Cov.: 33

Gnomad AFR AF: 0.294

Gnomad AMI AF: 0.515

Gnomad AMR AF: 0.474

Gnomad ASJ AF: 0.459

Gnomad EAS AF: 0.485

Gnomad SAS AF: 0.384

Gnomad FIN AF: 0.483

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.513

Gnomad OTH AF: 0.457

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

GnomAD4 genome AF: 0.440 AC: 66954 AN: 152104 Hom.: 15396 Cov.: 33 AF XY: 0.439 AC XY: 32662 AN XY: 74328

African (AFR) AF: 0.294 AC: 12209 AN: 41490

American (AMR) AF: 0.475 AC: 7249 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.459 AC: 1592 AN: 3470

East Asian (EAS) AF: 0.485 AC: 2508 AN: 5166

South Asian (SAS) AF: 0.383 AC: 1851 AN: 4828

European-Finnish (FIN) AF: 0.483 AC: 5110 AN: 10572

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.513 AC: 34869 AN: 67986

Other (OTH) AF: 0.460 AC: 971 AN: 2112

Alfa AF: 0.464 Hom.: 7930

Bravo AF: 0.436

Asia WGS AF: 0.452 AC: 1569 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.32
PhyloP100		0.081
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: rs723919; hg19: chr16-83342234;