rs6879762

Variant names:

• chr5-20448740-C-G
• rs6879762
• NM_001291956.3:c.-580+126722G>C

Variant summary

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

The NM_001291956.3(CDH18):​c.-580+126722G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.738 in 151,946 control chromosomes in the GnomAD database, including 41,689 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 0.74 (41689 hom., cov: 31)
• Consequence: CDH18 NM_001291956.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.191
• Publications: 1 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.832 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH18	NM_001291956.3	c.-580+126722G>C		intron_variant	Intron 1 of 14		NP_001278885.1
CDH18	NM_001349556.2	c.-434+126722G>C		intron_variant	Intron 1 of 13		NP_001336485.1
CDH18	NM_001349558.2	c.-727-110501G>C		intron_variant	Intron 1 of 15		NP_001336487.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH18	ENST00000507958.5	c.-580+126722G>C		intron_variant	Intron 1 of 14	2		ENSP00000425093.1
CDH18	ENST00000507632.2	n.402+126722G>C		intron_variant	Intron 1 of 2	4

Frequencies

GnomAD3 genomes AF: 0.738 AC: 112029 AN: 151828 Hom.: 41652 Cov.: 31

Gnomad AFR AF: 0.662

Gnomad AMI AF: 0.670

Gnomad AMR AF: 0.844

Gnomad ASJ AF: 0.844

Gnomad EAS AF: 0.692

Gnomad SAS AF: 0.767

Gnomad FIN AF: 0.735

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.756

Gnomad OTH AF: 0.771

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

GnomAD4 genome AF: 0.738 AC: 112116 AN: 151946 Hom.: 41689 Cov.: 31 AF XY: 0.741 AC XY: 55035 AN XY: 74258

African (AFR) AF: 0.662 AC: 27431 AN: 41412

American (AMR) AF: 0.844 AC: 12886 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.844 AC: 2928 AN: 3470

East Asian (EAS) AF: 0.692 AC: 3550 AN: 5132

South Asian (SAS) AF: 0.767 AC: 3697 AN: 4820

European-Finnish (FIN) AF: 0.735 AC: 7765 AN: 10558

Middle Eastern (MID) AF: 0.799 AC: 235 AN: 294

European-Non Finnish (NFE) AF: 0.756 AC: 51384 AN: 67976

Other (OTH) AF: 0.773 AC: 1629 AN: 2108

Alfa AF: 0.734 Hom.: 5094

Bravo AF: 0.741

Asia WGS AF: 0.727 AC: 2529 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.43
DANN	Benign	0.41
PhyloP100		-0.19
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6879762; hg19: chr5-20448849;