NM_001257.5:c.45+27055A>G

Variant names:

• chr16-82654192-A-G
• rs17177428
• NM_001257.5:c.45+27055A>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.45+27055A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.506 in 151,924 control chromosomes in the GnomAD database, including 19,905 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 0.51 (19905 hom., cov: 31)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11
• Publications: 3 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.631 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.45+27055A>G		intron	N/A	NP_001248.1
	CDH13	NM_001220488.2		c.186+14727A>G		intron	N/A	NP_001207417.1
	CDH13	NM_001220489.2		c.45+27055A>G		intron	N/A	NP_001207418.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH13	ENST00000567109.6	TSL:1 MANE Select	c.45+27055A>G		intron	N/A	ENSP00000479395.1
	CDH13	ENST00000431540.7	TSL:1	c.45+27055A>G		intron	N/A	ENSP00000408632.3
	CDH13	ENST00000567445.1	TSL:1	c.45+27055A>G		intron	N/A	ENSP00000456297.1

Frequencies

GnomAD3 genomes AF: 0.506 AC: 76824 AN: 151806 Hom.: 19871 Cov.: 31

Gnomad AFR AF: 0.637

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.486

Gnomad ASJ AF: 0.510

Gnomad EAS AF: 0.531

Gnomad SAS AF: 0.400

Gnomad FIN AF: 0.399

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.455

Gnomad OTH AF: 0.530

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

GnomAD4 genome AF: 0.506 AC: 76907 AN: 151924 Hom.: 19905 Cov.: 31 AF XY: 0.501 AC XY: 37201 AN XY: 74226

African (AFR) AF: 0.637 AC: 26389 AN: 41416

American (AMR) AF: 0.485 AC: 7419 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.510 AC: 1766 AN: 3466

East Asian (EAS) AF: 0.531 AC: 2731 AN: 5140

South Asian (SAS) AF: 0.401 AC: 1924 AN: 4804

European-Finnish (FIN) AF: 0.399 AC: 4214 AN: 10560

Middle Eastern (MID) AF: 0.517 AC: 151 AN: 292

European-Non Finnish (NFE) AF: 0.455 AC: 30893 AN: 67956

Other (OTH) AF: 0.528 AC: 1108 AN: 2100

Alfa AF: 0.404 Hom.: 1983

Bravo AF: 0.522

Asia WGS AF: 0.436 AC: 1516 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.11
DANN	Benign	0.35
PhyloP100		-1.1
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: rs17177428; hg19: chr16-82687797;