Variant chr5-141864791-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_032420.5(PCDH1):c.1540G>A(p.Ala514Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.072 in 1,614,012 control chromosomes in the GnomAD database, including 4,887 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.068 ( 465 hom., cov: 32)

Exomes 𝑓: 0.072 ( 4422 hom. )

Consequence

PCDH1
NM_032420.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.12

Variant links:

Genes affected

PCDH1 (HGNC:8655): (protocadherin 1) This gene belongs to the protocadherin subfamily within the cadherin superfamily. The encoded protein is a membrane protein found at cell-cell boundaries. It is involved in neural cell adhesion, suggesting a possible role in neuronal development. The protein includes an extracelllular region, containing 7 cadherin-like domains, a transmembrane region and a C-terminal cytoplasmic region. Cells expressing the protein showed cell aggregation activity. Alternative splicing occurs in this gene. [provided by RefSeq, Jul 2008]

PCDH1 links:

PCDH1 (HGNC:):

PCDH1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.001683265).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCDH1	NM_032420.5 linkuse as main transcript	c.1540G>A	p.Ala514Thr	missense_variant	3/5	ENST00000287008.8	NP_115796.2	Q08174-2B4E2D8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCDH1	ENST00000287008.8 linkuse as main transcript	c.1540G>A	p.Ala514Thr	missense_variant	3/5	5	NM_032420.5	ENSP00000287008.3		Q08174-2

Frequencies

GnomAD3 genomes

AF:

0.0682

AC:

10373

AN:

152018

Hom.:

461

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0358

Gnomad AMI

AF:

0.0603

Gnomad AMR

AF:

0.126

Gnomad ASJ

AF:

0.0427

Gnomad EAS

AF:

0.144

Gnomad SAS

AF:

0.115

Gnomad FIN

AF:

0.0907

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.0637

Gnomad OTH

AF:

0.0685

GnomAD3 exomes

AF:

0.0913

AC:

22940

AN:

251328

Hom.:

1339

AF XY:

0.0903

AC XY:

12267

AN XY:

135836

show subpopulations

Gnomad AFR exome

AF:

0.0356

Gnomad AMR exome

AF:

0.165

Gnomad ASJ exome

AF:

0.0458

Gnomad EAS exome

AF:

0.138

Gnomad SAS exome

AF:

0.119

Gnomad FIN exome

AF:

0.101

Gnomad NFE exome

AF:

0.0642

Gnomad OTH exome

AF:

0.0847

GnomAD4 exome

AF:

0.0724

AC:

105888

AN:

1461874

Hom.:

4422

Cov.:

AF XY:

0.0733

AC XY:

53317

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.0345

Gnomad4 AMR exome

AF:

0.162

Gnomad4 ASJ exome

AF:

0.0436

Gnomad4 EAS exome

AF:

0.141

Gnomad4 SAS exome

AF:

0.116

Gnomad4 FIN exome

AF:

0.101

Gnomad4 NFE exome

AF:

0.0634

Gnomad4 OTH exome

AF:

0.0736

GnomAD4 genome

AF:

0.0683

AC:

10391

AN:

152138

Hom.:

465

Cov.:

AF XY:

0.0723

AC XY:

5374

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.0357

Gnomad4 AMR

AF:

0.127

Gnomad4 ASJ

AF:

0.0427

Gnomad4 EAS

AF:

0.145

Gnomad4 SAS

AF:

0.116

Gnomad4 FIN

AF:

0.0907

Gnomad4 NFE

AF:

0.0637

Gnomad4 OTH

AF:

0.0692

Alfa

AF:

0.0666

Hom.:

979

Bravo

AF:

0.0695

TwinsUK

AF:

0.0645

AC:

239

ALSPAC

AF:

0.0610

AC:

235

ESP6500AA

AF:

0.0359

AC:

158

ESP6500EA

AF:

0.0606

AC:

521

ExAC

AF:

0.0866

AC:

10519

Asia WGS

AF:

0.121

AC:

420

AN:

3478

EpiCase

AF:

0.0625

EpiControl

AF:

0.0608

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.020

.;T

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.12

FATHMM_MKL

Benign

0.59

LIST_S2

Benign

0.77

T;T

MetaRNN

Benign

0.0017

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.40

N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.59

N;N

REVEL

Benign

0.084

Sift

Benign

0.14

T;T

Sift4G

Benign

0.42

T;T

Polyphen

0.94

P;P

Vest4

0.022

MPC

0.45

ClinPred

0.011

GERP RS

3.9

Varity_R

0.058

gMVP

0.097

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over