Variant 18-65809970-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_004361.5(CDH7):c.477G>A(p.Thr159=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.02 in 1,611,472 control chromosomes in the GnomAD database, including 678 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.020 ( 88 hom., cov: 31)

Exomes 𝑓: 0.020 ( 590 hom. )

Consequence

CDH7
NM_004361.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.62

Variant links:

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]

CDH7 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 18-65809970-G-A is Benign according to our data. Variant chr18-65809970-G-A is described in ClinVar as [Benign]. Clinvar id is 1244452.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.62 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0693 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CDH7	NM_004361.5 linkuse as main transcript	c.477G>A	p.Thr159=	synonymous_variant	3/12	ENST00000397968.4
CDH7	NM_001362438.2 linkuse as main transcript	c.477G>A	p.Thr159=	synonymous_variant	3/12
CDH7	NM_033646.4 linkuse as main transcript	c.477G>A	p.Thr159=	synonymous_variant	3/12
CDH7	NM_001317214.3 linkuse as main transcript	c.477G>A	p.Thr159=	synonymous_variant	3/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
CDH7	ENST00000397968.4 linkuse as main transcript	c.477G>A	p.Thr159=	synonymous_variant	3/12	1	NM_004361.5	P1
CDH7	ENST00000323011.7 linkuse as main transcript	c.477G>A	p.Thr159=	synonymous_variant	3/12	1		P1
CDH7	ENST00000536984.6 linkuse as main transcript	c.477G>A	p.Thr159=	synonymous_variant	3/11	1

Frequencies

GnomAD3 genomes

AF:

0.0204

AC:

3104

AN:

151952

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00452

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.0726

Gnomad ASJ

AF:

0.00922

Gnomad EAS

AF:

0.000968

Gnomad SAS

AF:

0.00954

Gnomad FIN

AF:

0.0294

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0200

Gnomad OTH

AF:

0.0211

GnomAD3 exomes

AF:

0.0302

AC:

7566

AN:

250168

Hom.:

341

AF XY:

0.0265

AC XY:

3584

AN XY:

135336

show subpopulations

Gnomad AFR exome

AF:

0.00389

Gnomad AMR exome

AF:

0.121

Gnomad ASJ exome

AF:

0.00755

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00986

Gnomad FIN exome

AF:

0.0352

Gnomad NFE exome

AF:

0.0181

Gnomad OTH exome

AF:

0.0250

GnomAD4 exome

AF:

0.0200

AC:

29127

AN:

1459402

Hom.:

590

Cov.:

AF XY:

0.0195

AC XY:

14153

AN XY:

725486

show subpopulations

Gnomad4 AFR exome

AF:

0.00311

Gnomad4 AMR exome

AF:

0.115

Gnomad4 ASJ exome

AF:

0.00873

Gnomad4 EAS exome

AF:

0.0000757

Gnomad4 SAS exome

AF:

0.0108

Gnomad4 FIN exome

AF:

0.0318

Gnomad4 NFE exome

AF:

0.0181

Gnomad4 OTH exome

AF:

0.0160

GnomAD4 genome

AF:

0.0204

AC:

3109

AN:

152070

Hom.:

Cov.:

AF XY:

0.0218

AC XY:

1624

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.00451

Gnomad4 AMR

AF:

0.0728

Gnomad4 ASJ

AF:

0.00922

Gnomad4 EAS

AF:

0.000970

Gnomad4 SAS

AF:

0.00976

Gnomad4 FIN

AF:

0.0294

Gnomad4 NFE

AF:

0.0200

Gnomad4 OTH

AF:

0.0208

Alfa

AF:

0.0178

Hom.:

Bravo

AF:

0.0232

Asia WGS

AF:

0.0120

AC:

AN:

3478

EpiCase

AF:

0.0171

EpiControl

AF:

0.0143

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 09, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.089

DANN

Benign

0.81

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over