Variant chr18-65762926-A-G 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.84A>G(p.Glu28=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00539 in 1,613,538 control chromosomes in the GnomAD database, including 379 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.028 ( 190 hom., cov: 32)

Exomes 𝑓: 0.0030 ( 189 hom. )

Consequence

CDH7
NM_004361.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.523

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 18-65762926-A-G is Benign according to our data. Variant chr18-65762926-A-G is described in ClinVar as [Benign]. Clinvar id is 773074.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.523 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0936 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CDH7	NM_004361.5 linkuse as main transcript	c.84A>G	p.Glu28=	synonymous_variant	2/12	ENST00000397968.4
CDH7	NM_001362438.2 linkuse as main transcript	c.84A>G	p.Glu28=	synonymous_variant	2/12
CDH7	NM_033646.4 linkuse as main transcript	c.84A>G	p.Glu28=	synonymous_variant	2/12
CDH7	NM_001317214.3 linkuse as main transcript	c.84A>G	p.Glu28=	synonymous_variant	2/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
CDH7	ENST00000397968.4 linkuse as main transcript	c.84A>G	p.Glu28=	synonymous_variant	2/12	1	NM_004361.5	P1
CDH7	ENST00000323011.7 linkuse as main transcript	c.84A>G	p.Glu28=	synonymous_variant	2/12	1		P1
CDH7	ENST00000536984.6 linkuse as main transcript	c.84A>G	p.Glu28=	synonymous_variant	2/11	1

Frequencies

GnomAD3 genomes

AF:

0.0281

AC:

4271

AN:

151984

Hom.:

190

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0960

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0148

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000353

Gnomad OTH

AF:

0.0216

GnomAD3 exomes

AF:

0.00757

AC:

1903

AN:

251238

Hom.:

AF XY:

0.00558

AC XY:

758

AN XY:

135790

show subpopulations

Gnomad AFR exome

AF:

0.0983

Gnomad AMR exome

AF:

0.00681

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000378

Gnomad OTH exome

AF:

0.00391

GnomAD4 exome

AF:

0.00302

AC:

4419

AN:

1461436

Hom.:

189

Cov.:

AF XY:

0.00266

AC XY:

1937

AN XY:

727054

show subpopulations

Gnomad4 AFR exome

AF:

0.100

Gnomad4 AMR exome

AF:

0.00725

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000151

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000212

Gnomad4 OTH exome

AF:

0.00760

GnomAD4 genome

AF:

0.0282

AC:

4284

AN:

152102

Hom.:

190

Cov.:

AF XY:

0.0264

AC XY:

1961

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.0961

Gnomad4 AMR

AF:

0.0148

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000416

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000353

Gnomad4 OTH

AF:

0.0214

Alfa

AF:

0.00714

Hom.:

Bravo

AF:

0.0331

Asia WGS

AF:

0.00549

AC:

AN:

3478

EpiCase

AF:

0.000709

EpiControl

AF:

0.000830

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	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 04, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

1.6

DANN

Benign

0.56

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