18-65814178-A-T

Position:

• chr18-65814178-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004361.5(CDH7):​c.506-307A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 151,946 control chromosomes in the GnomAD database, including 4,098 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.22 (4098 hom., cov: 31)
• Consequence: CDH7 NM_004361.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.46

Genes affected

CDH7 (HGNC:1766): (cadherin 7) This gene encodes a type II classical cadherin of the cadherin superfamily. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate the mature glycoprotein. This calcium dependent cell-cell adhesion molecule is comprised of five extracellular cadherin repeats, a transmembrane region and a highly conserved cytoplasmic tail. Type II (atypical) cadherins are defined based on their lack of a histidine-alanine-valine (HAV) cell adhesion recognition sequence specific to type I cadherins. Cadherins mediate cell-cell binding in a homophilic manner, contributing to the sorting of heterogeneous cell types. Mutations in this gene may be associated with bipolar disease in human patients. This gene is present in a gene cluster on chromosome 18. [provided by RefSeq, May 2016]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 18-65814178-A-T is Benign according to our data. Variant chr18-65814178-A-T is described in ClinVar as [Benign]. Clinvar id is 1282023.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDH7	NM_004361.5	c.506-307A>T		intron_variant		ENST00000397968.4
CDH7	NM_001317214.3	c.506-307A>T		intron_variant
CDH7	NM_001362438.2	c.506-307A>T		intron_variant
CDH7	NM_033646.4	c.506-307A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH7	ENST00000397968.4	c.506-307A>T		intron_variant		1	NM_004361.5	P1
CDH7	ENST00000323011.7	c.506-307A>T		intron_variant		1		P1
CDH7	ENST00000536984.6	c.506-307A>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34073 AN: 151828 Hom.: 4094 Cov.: 31

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.0212

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.280

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.221

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

GnomAD4 genome AF: 0.224 AC: 34095 AN: 151946 Hom.: 4098 Cov.: 31 AF XY: 0.221 AC XY: 16423 AN XY: 74242

Gnomad4 AFR AF: 0.173

Gnomad4 AMR AF: 0.231

Gnomad4 ASJ AF: 0.153

Gnomad4 EAS AF: 0.0209

Gnomad4 SAS AF: 0.174

Gnomad4 FIN AF: 0.280

Gnomad4 NFE AF: 0.270

Gnomad4 OTH AF: 0.221

Alfa AF: 0.164 Hom.: 344

Bravo AF: 0.217

Asia WGS AF: 0.134 AC: 467 AN: 3478

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

GeneDx

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.1
DANN	Benign	0.79

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: rs7228436; hg19: chr18-63481414;