18-65822425-G-A

Variant names:

• chr18-65822425-G-A
• rs9955096
• NM_004361.5:c.793+177G>A

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.793+177G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 151,568 control chromosomes in the GnomAD database, including 3,359 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.20 (3359 hom., cov: 32)
• Consequence: CDH7 NM_004361.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.971
• Publications: 3 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=-0.83).
• BP6: Variant 18-65822425-G-A is Benign according to our data. Variant chr18-65822425-G-A is described in ClinVar as [Benign]. Clinvar id is 1270991.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH7	NM_004361.5	c.793+177G>A		intron_variant	Intron 5 of 11	ENST00000397968.4	NP_004352.2
CDH7	NM_001362438.2	c.793+177G>A		intron_variant	Intron 5 of 11		NP_001349367.1
CDH7	NM_033646.4	c.793+177G>A		intron_variant	Intron 5 of 11		NP_387450.1
CDH7	NM_001317214.3	c.793+177G>A		intron_variant	Intron 5 of 10		NP_001304143.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH7	ENST00000397968.4	c.793+177G>A		intron_variant	Intron 5 of 11	1	NM_004361.5	ENSP00000381058.2
CDH7	ENST00000323011.7	c.793+177G>A		intron_variant	Intron 5 of 11	1		ENSP00000319166.3
CDH7	ENST00000536984.6	c.793+177G>A		intron_variant	Intron 5 of 10	1		ENSP00000443030.2

Frequencies

GnomAD3 genomes AF: 0.205 AC: 31012 AN: 151456 Hom.: 3355 Cov.: 32

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.167

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.144

Gnomad EAS AF: 0.0202

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.254

Gnomad MID AF: 0.156

Gnomad NFE AF: 0.250

Gnomad OTH AF: 0.200

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

GnomAD4 genome AF: 0.205 AC: 31029 AN: 151568 Hom.: 3359 Cov.: 32 AF XY: 0.200 AC XY: 14837 AN XY: 74012

African (AFR) AF: 0.169 AC: 7008 AN: 41372

American (AMR) AF: 0.158 AC: 2406 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 498 AN: 3464

East Asian (EAS) AF: 0.0198 AC: 102 AN: 5140

South Asian (SAS) AF: 0.165 AC: 792 AN: 4804

European-Finnish (FIN) AF: 0.254 AC: 2658 AN: 10464

Middle Eastern (MID) AF: 0.164 AC: 48 AN: 292

European-Non Finnish (NFE) AF: 0.250 AC: 16943 AN: 67796

Other (OTH) AF: 0.200 AC: 422 AN: 2108

Alfa AF: 0.201 Hom.: 1803

Bravo AF: 0.193

Asia WGS AF: 0.121 AC: 421 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	-0.83
CADD	Benign	0.26
DANN	Benign	0.16
PhyloP100		-0.97
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs9955096; hg19: chr18-63489661;