rs995021

Variant names:

• chr5-20458796-G-A
• rs995021
• NM_001291956.3:c.-580+116666C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-20458796-G-A
• chr5-20458796-G-C
• chr5-20458796-G-T

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+116666C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.572 in 152,008 control chromosomes in the GnomAD database, including 25,700 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 0.57 (25700 hom., cov: 33)
• Consequence: CDH18 NM_001291956.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.733
• 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.698 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001291956.3. 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
	CDH18	NM_001291956.3		c.-580+116666C>T		intron	N/A	NP_001278885.1
	CDH18	NM_001349556.2		c.-434+116666C>T		intron	N/A	NP_001336485.1
	CDH18	NM_001349558.2		c.-728+116666C>T		intron	N/A	NP_001336487.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH18	ENST00000507958.5	TSL:2	c.-580+116666C>T		intron	N/A	ENSP00000425093.1
	CDH18	ENST00000507632.2	TSL:4	n.402+116666C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.572 AC: 86843 AN: 151888 Hom.: 25663 Cov.: 33

Gnomad AFR AF: 0.704

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.532

Gnomad ASJ AF: 0.619

Gnomad EAS AF: 0.298

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.545

Gnomad OTH AF: 0.567

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

GnomAD4 genome AF: 0.572 AC: 86942 AN: 152008 Hom.: 25700 Cov.: 33 AF XY: 0.565 AC XY: 41987 AN XY: 74294

African (AFR) AF: 0.704 AC: 29210 AN: 41466

American (AMR) AF: 0.532 AC: 8118 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.619 AC: 2148 AN: 3468

East Asian (EAS) AF: 0.298 AC: 1540 AN: 5170

South Asian (SAS) AF: 0.472 AC: 2277 AN: 4820

European-Finnish (FIN) AF: 0.463 AC: 4893 AN: 10564

Middle Eastern (MID) AF: 0.558 AC: 163 AN: 292

European-Non Finnish (NFE) AF: 0.544 AC: 36997 AN: 67950

Other (OTH) AF: 0.568 AC: 1200 AN: 2112

Alfa AF: 0.441 Hom.: 1638

Bravo AF: 0.582

Asia WGS AF: 0.432 AC: 1506 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.4
DANN	Benign	0.20
PhyloP100		0.73
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: rs995021; hg19: chr5-20458905;