5-19929179-C-T

Position:

• chr5-19929179-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004934.5(CDH18):​c.-257+51881G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 152,028 control chromosomes in the GnomAD database, including 3,823 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 0.13 (3823 hom., cov: 32)
• Consequence: CDH18 NM_004934.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0110

Genes affected

CDH18 (HGNC:1757): (cadherin 18) This gene encodes a type II classical cadherin from the cadherin superfamily of integral membrane proteins that mediate calcium-dependent cell-cell adhesion. Mature cadherin proteins are composed of a large N-terminal extracellular domain, a single membrane-spanning domain, and a small, highly conserved C-terminal cytoplasmic domain. Type II (atypical) cadherins are defined based on their lack of a HAV cell adhesion recognition sequence specific to type I cadherins. This particular cadherin is expressed specifically in the central nervous system and is putatively involved in synaptic adhesion, axon outgrowth and guidance. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.409 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDH18	NM_004934.5	c.-257+51881G>A		intron_variant		ENST00000382275.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH18	ENST00000382275.6	c.-257+51881G>A		intron_variant		1	NM_004934.5	P1

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20414 AN: 151910 Hom.: 3804 Cov.: 32

Gnomad AFR AF: 0.414

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0845

Gnomad ASJ AF: 0.0435

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.0201

Gnomad FIN AF: 0.0150

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.00366

Gnomad OTH AF: 0.122

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

GnomAD4 genome AF: 0.135 AC: 20486 AN: 152028 Hom.: 3823 Cov.: 32 AF XY: 0.133 AC XY: 9893 AN XY: 74308

Gnomad4 AFR AF: 0.414

Gnomad4 AMR AF: 0.0848

Gnomad4 ASJ AF: 0.0435

Gnomad4 EAS AF: 0.217

Gnomad4 SAS AF: 0.0203

Gnomad4 FIN AF: 0.0150

Gnomad4 NFE AF: 0.00366

Gnomad4 OTH AF: 0.121

Alfa AF: 0.0271 Hom.: 878

Bravo AF: 0.154

Asia WGS AF: 0.126 AC: 439 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.9
DANN	Benign	0.58

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

Publications

LitVar

Other links and lift over

dbSNP: rs1911845; hg19: chr5-19929288;