16-83031764-G-C

Variant names:

• chr16-83031764-G-C
• rs35178368
• NM_001257.5:c.158-246G>C

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.158-246G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 152,150 control chromosomes in the GnomAD database, including 1,530 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.13 (1530 hom., cov: 30)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.15
• Publications: 0 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 16-83031764-G-C is Benign according to our data. Variant chr16-83031764-G-C is described in ClinVar as Benign. ClinVar VariationId is 1253546.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.255 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.158-246G>C		intron	N/A	NP_001248.1	P55290-1
	CDH13	NM_001220488.2		c.299-246G>C		intron	N/A	NP_001207417.1	P55290-4
	CDH13	NM_001220489.2		c.158-246G>C		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.158-246G>C		intron	N/A	ENSP00000479395.1	P55290-1
	CDH13	ENST00000431540.7	TSL:1	c.158-246G>C		intron	N/A	ENSP00000408632.3	P55290-2
	CDH13	ENST00000268613.14	TSL:2	c.299-246G>C		intron	N/A	ENSP00000268613.10	P55290-4

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19668 AN: 152032 Hom.: 1531 Cov.: 30

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.170

Gnomad EAS AF: 0.268

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.0718

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.0896

Gnomad OTH AF: 0.124

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

GnomAD4 genome AF: 0.129 AC: 19678 AN: 152150 Hom.: 1530 Cov.: 30 AF XY: 0.130 AC XY: 9686 AN XY: 74386

African (AFR) AF: 0.180 AC: 7487 AN: 41504

American (AMR) AF: 0.134 AC: 2056 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.170 AC: 590 AN: 3470

East Asian (EAS) AF: 0.267 AC: 1372 AN: 5136

South Asian (SAS) AF: 0.208 AC: 1004 AN: 4820

European-Finnish (FIN) AF: 0.0718 AC: 761 AN: 10600

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.0896 AC: 6096 AN: 68012

Other (OTH) AF: 0.122 AC: 257 AN: 2108

Alfa AF: 0.0210 Hom.: 9

Bravo AF: 0.138

Asia WGS AF: 0.214 AC: 746 AN: 3478

ClinVar

ClinVar submissions

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	-0.97
CADD	Benign	0.19
DANN	Benign	0.70
PhyloP100		-2.2
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: rs35178368; hg19: chr16-83065369;