5-19571674-A-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_004934.5(CDH18):c.1158T>G(p.Pro386=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00348 in 1,613,816 control chromosomes in the GnomAD database, including 64 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0093 (14 hom., cov: 32)
  • Exomes 𝑓: 0.0029 (50 hom.)
• Consequence: CDH18 NM_004934.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.208

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 5-19571674-A-C is Benign according to our data. Variant chr5-19571674-A-C is described in ClinVar as [Benign]. Clinvar id is 767995.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.208 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00934 (1421/152198) while in subpopulation AFR AF= 0.0262 (1087/41520). AF 95% confidence interval is 0.0249. There are 14 homozygotes in gnomad4. There are 676 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 13 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDH18	NM_004934.5	c.1158T>G	p.Pro386=	synonymous_variant	8/13	ENST00000382275.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH18	ENST00000382275.6	c.1158T>G	p.Pro386=	synonymous_variant	8/13	1	NM_004934.5	P1

Frequencies

GnomAD3 genomes AF: 0.00930 AC: 1415 AN: 152080 Hom.: 13 Cov.: 32

Gnomad AFR AF: 0.0261

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.00498

Gnomad ASJ AF: 0.0251

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00726

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.00131

Gnomad OTH AF: 0.0134

GnomAD3 exomes AF: 0.00537 AC: 1347 AN: 250974 Hom.: 12 AF XY: 0.00524 AC XY: 711 AN XY: 135620

Gnomad AFR exome AF: 0.0263

Gnomad AMR exome AF: 0.00581

Gnomad ASJ exome AF: 0.0209

Gnomad EAS exome AF: 0.0000545

Gnomad SAS exome AF: 0.00791

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00196

Gnomad OTH exome AF: 0.00718

GnomAD4 exome AF: 0.00287 AC: 4201 AN: 1461618 Hom.: 50 Cov.: 31 AF XY: 0.00303 AC XY: 2201 AN XY: 727112

Gnomad4 AFR exome AF: 0.0281

Gnomad4 AMR exome AF: 0.00555

Gnomad4 ASJ exome AF: 0.0208

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00698

Gnomad4 FIN exome AF: 0.000131

Gnomad4 NFE exome AF: 0.00110

Gnomad4 OTH exome AF: 0.00578

GnomAD4 genome AF: 0.00934 AC: 1421 AN: 152198 Hom.: 14 Cov.: 32 AF XY: 0.00908 AC XY: 676 AN XY: 74414

Gnomad4 AFR AF: 0.0262

Gnomad4 AMR AF: 0.00497

Gnomad4 ASJ AF: 0.0251

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00747

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00131

Gnomad4 OTH AF: 0.0132

Alfa AF: 0.00551 Hom.: 2

Bravo AF: 0.0103

Asia WGS AF: 0.00404 AC: 14 AN: 3478

EpiCase AF: 0.00273

EpiControl AF: 0.00379

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
Cadd	Benign	5.9
Dann	Benign	0.69

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: rs78589740; hg19: chr5-19571783;