Variant 20-61254848-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001794.5(CDH4):c.80C>T(p.Thr27Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00113 in 1,609,218 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0023 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0010 ( 7 hom. )

Consequence

CDH4
NM_001794.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.668

Variant links:

Genes affected

CDH4 (HGNC:1763): (cadherin 4) This gene is a classical cadherin from the cadherin superfamily. The encoded protein is a calcium-dependent cell-cell adhesion glycoprotein comprised of five extracellular cadherin repeats, a transmembrane region and a highly conserved cytoplasmic tail. Based on studies in chicken and mouse, this cadherin is thought to play an important role during brain segmentation and neuronal outgrowth. In addition, a role in kidney and muscle development is indicated. Of particular interest are studies showing stable cis-heterodimers of cadherins 2 and 4 in cotransfected cell lines. Previously thought to interact in an exclusively homophilic manner, this is the first evidence of cadherin heterodimerization. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2011]

CDH4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009611875).

BP6

Variant 20-61254848-C-T is Benign according to our data. Variant chr20-61254848-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 775438.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd at 352 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CDH4	NM_001794.5 linkuse as main transcript	c.80C>T	p.Thr27Ile	missense_variant	2/16	ENST00000614565.5
CDH4	XM_047439812.1 linkuse as main transcript	c.-143C>T		5_prime_UTR_variant	2/16
CDH4	XM_047439813.1 linkuse as main transcript	c.-143C>T		5_prime_UTR_variant	2/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH4	ENST00000614565.5 linkuse as main transcript	c.80C>T	p.Thr27Ile	missense_variant	2/16	1	NM_001794.5	P1	P55283-1

Frequencies

GnomAD3 genomes

AF:

0.00231

AC:

352

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00577

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00229

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.000750

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00123

AC:

310

AN:

251448

Hom.:

AF XY:

0.00127

AC XY:

173

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.00542

Gnomad AMR exome

AF:

0.00171

Gnomad ASJ exome

AF:

0.00298

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000967

Gnomad OTH exome

AF:

0.00326

GnomAD4 exome

AF:

0.00101

AC:

1470

AN:

1456902

Hom.:

Cov.:

AF XY:

0.00105

AC XY:

758

AN XY:

725166

show subpopulations

Gnomad4 AFR exome

AF:

0.00719

Gnomad4 AMR exome

AF:

0.00197

Gnomad4 ASJ exome

AF:

0.00264

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000151

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000724

Gnomad4 OTH exome

AF:

0.00284

GnomAD4 genome

AF:

0.00232

AC:

353

AN:

152316

Hom.:

Cov.:

AF XY:

0.00224

AC XY:

167

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.00577

Gnomad4 AMR

AF:

0.00222

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000750

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00123

Hom.:

Bravo

AF:

0.00276

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00431

AC:

ESP6500EA

AF:

0.00105

AC:

ExAC

AF:

0.00129

AC:

157

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.00169

EpiControl

AF:

0.00136

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Nov 19, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.51

Cadd

Benign

Dann

Uncertain

0.98

DEOGEN2

Benign

0.067

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.30

FATHMM_MKL

Benign

0.44

LIST_S2

Benign

0.43

MetaRNN

Benign

0.0096

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.46

Sift4G

Benign

0.14

Polyphen

0.0

Vest4

0.28

MVP

0.29

ClinPred

0.015

GERP RS

1.2

Varity_R

0.037

gMVP

0.18

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

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