16-83135094-G-C

Variant names:

• chr16-83135094-G-C
• rs8054536
• NM_001257.5:c.483+9593G>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.483+9593G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.52 in 152,072 control chromosomes in the GnomAD database, including 22,414 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 0.52 (22414 hom., cov: 32)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.587
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.753 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.483+9593G>C		intron	N/A	NP_001248.1
	CDH13	NM_001220488.2		c.624+9593G>C		intron	N/A	NP_001207417.1
	CDH13	NM_001220489.2		c.367-82251G>C		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.483+9593G>C		intron	N/A	ENSP00000479395.1
	CDH13	ENST00000431540.7	TSL:1	c.483+9593G>C		intron	N/A	ENSP00000408632.3
	CDH13	ENST00000268613.14	TSL:2	c.624+9593G>C		intron	N/A	ENSP00000268613.10

Frequencies

GnomAD3 genomes AF: 0.519 AC: 78935 AN: 151954 Hom.: 22373 Cov.: 32

Gnomad AFR AF: 0.760

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.482

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.320

Gnomad SAS AF: 0.434

Gnomad FIN AF: 0.460

Gnomad MID AF: 0.327

Gnomad NFE AF: 0.427

Gnomad OTH AF: 0.476

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

GnomAD4 genome AF: 0.520 AC: 79032 AN: 152072 Hom.: 22414 Cov.: 32 AF XY: 0.516 AC XY: 38371 AN XY: 74320

African (AFR) AF: 0.760 AC: 31531 AN: 41484

American (AMR) AF: 0.482 AC: 7365 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.344 AC: 1193 AN: 3472

East Asian (EAS) AF: 0.320 AC: 1656 AN: 5168

South Asian (SAS) AF: 0.432 AC: 2078 AN: 4808

European-Finnish (FIN) AF: 0.460 AC: 4860 AN: 10570

Middle Eastern (MID) AF: 0.332 AC: 97 AN: 292

European-Non Finnish (NFE) AF: 0.427 AC: 29020 AN: 67968

Other (OTH) AF: 0.474 AC: 1002 AN: 2112

Alfa AF: 0.322 Hom.: 785

Bravo AF: 0.530

Asia WGS AF: 0.425 AC: 1479 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.83
DANN	Benign	0.63
PhyloP100		-0.59
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: rs8054536; hg19: chr16-83168699;