rs66550127

Variant names:

• chr18-65821778-A-G
• rs66550127
• NM_004361.5:c.626-303A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004361.5(CDH7):​c.626-303A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 152,096 control chromosomes in the GnomAD database, including 3,511 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.21 (3511 hom., cov: 33)
• Consequence: CDH7 NM_004361.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0530
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 18-65821778-A-G is Benign according to our data. Variant chr18-65821778-A-G is described in ClinVar as [Benign]. Clinvar id is 1224024.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH7	NM_004361.5	c.626-303A>G		intron_variant	Intron 4 of 11	ENST00000397968.4	NP_004352.2
CDH7	NM_001362438.2	c.626-303A>G		intron_variant	Intron 4 of 11		NP_001349367.1
CDH7	NM_033646.4	c.626-303A>G		intron_variant	Intron 4 of 11		NP_387450.1
CDH7	NM_001317214.3	c.626-303A>G		intron_variant	Intron 4 of 10		NP_001304143.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH7	ENST00000397968.4	c.626-303A>G		intron_variant	Intron 4 of 11	1	NM_004361.5	ENSP00000381058.2
CDH7	ENST00000323011.7	c.626-303A>G		intron_variant	Intron 4 of 11	1		ENSP00000319166.3
CDH7	ENST00000536984.6	c.626-303A>G		intron_variant	Intron 4 of 10	1		ENSP00000443030.2

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31655 AN: 151978 Hom.: 3507 Cov.: 33

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.167

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.0202

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.251

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.211

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

GnomAD4 genome AF: 0.208 AC: 31670 AN: 152096 Hom.: 3511 Cov.: 33 AF XY: 0.204 AC XY: 15149 AN XY: 74338

African (AFR) AF: 0.170 AC: 7040 AN: 41526

American (AMR) AF: 0.166 AC: 2536 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 575 AN: 3470

East Asian (EAS) AF: 0.0199 AC: 103 AN: 5186

South Asian (SAS) AF: 0.166 AC: 802 AN: 4820

European-Finnish (FIN) AF: 0.251 AC: 2652 AN: 10560

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.255 AC: 17311 AN: 67944

Other (OTH) AF: 0.211 AC: 445 AN: 2110

Alfa AF: 0.249 Hom.: 2069

Bravo AF: 0.198

Asia WGS AF: 0.124 AC: 432 AN: 3470

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.9
DANN	Benign	0.47
PhyloP100		-0.053
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs66550127; hg19: chr18-63489014;