5-141122501-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_018938.4(PCDHB4):c.503A>G(p.Lys168Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00372 in 1,614,230 control chromosomes in the GnomAD database, including 149 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.018 ( 76 hom., cov: 32)

Exomes 𝑓: 0.0023 ( 73 hom. )

Consequence

PCDHB4
NM_018938.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.34

Publications

5 publications found

Variant links:

Genes affected

PCDHB4 (HGNC:8689): (protocadherin beta 4) This gene is a member of the protocadherin beta gene cluster, one of three related gene clusters tandemly linked on chromosome five. The gene clusters demonstrate an unusual genomic organization similar to that of B-cell and T-cell receptor gene clusters. The beta cluster contains 16 genes and 3 pseudogenes, each encoding 6 extracellular cadherin domains and a cytoplasmic tail that deviates from others in the cadherin superfamily. The extracellular domains interact in a homophilic manner to specify differential cell-cell connections. Unlike the alpha and gamma clusters, the transcripts from these genes are made up of only one large exon, not sharing common 3' exons as expected. These neural cadherin-like cell adhesion proteins are integral plasma membrane proteins. Their specific functions are unknown but they most likely play a critical role in the establishment and function of specific cell-cell neural connections. [provided by RefSeq, Jul 2008]

PCDHB4 links:

PCDHB@ (HGNC:8679):

PCDHB@ links:

ENSG00000272154 (HGNC:):

ENSG00000272154 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0026776195).

BP6

Variant 5-141122501-A-G is Benign according to our data. Variant chr5-141122501-A-G is described in ClinVar as [Benign]. Clinvar id is 780568.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0567 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCDHB4	NM_018938.4 link	c.503A>G	p.Lys168Arg	missense_variant	Exon 1 of 1	ENST00000194152.4	NP_061761.1	Q9Y5E5
PCDHB@		n.141122501A>G		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCDHB4	ENST00000194152.4 link	c.503A>G	p.Lys168Arg	missense_variant	Exon 1 of 1	6	NM_018938.4	ENSP00000194152.1		Q9Y5E5

Frequencies

GnomAD3 genomes

AF:

0.0176

AC:

2675

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0587

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0101

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.000603

Gnomad OTH

AF:

0.0143

GnomAD2 exomes

AF:

0.00619

AC:

1556

AN:

251448

AF XY:

0.00455

show subpopulations

Gnomad AFR exome

AF:

0.0642

Gnomad AMR exome

AF:

0.00974

Gnomad ASJ exome

AF:

0.00288

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000747

Gnomad OTH exome

AF:

0.00961

GnomAD4 exome

AF:

0.00227

AC:

3325

AN:

1461886

Hom.:

Cov.:

AF XY:

0.00199

AC XY:

1445

AN XY:

727240

show subpopulations

African (AFR)

AF:

0.0597

AC:

1999

AN:

33478

American (AMR)

AF:

0.00970

AC:

434

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00256

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000812

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.0000374

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00711

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000451

AC:

501

AN:

1112012

Other (OTH)

AF:

0.00454

AC:

274

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

214

428

642

856

1070

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0176

AC:

2681

AN:

152344

Hom.:

Cov.:

AF XY:

0.0168

AC XY:

1250

AN XY:

74494

show subpopulations

African (AFR)

AF:

0.0587

AC:

2438

AN:

41568

American (AMR)

AF:

0.0101

AC:

155

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00317

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.000207

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000603

AC:

AN:

68040

Other (OTH)

AF:

0.0142

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

127

254

382

509

636

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00738

Hom.:

Bravo

AF:

0.0203

ESP6500AA

AF:

0.0617

AC:

272

ESP6500EA

AF:

0.000930

AC:

ExAC

AF:

0.00717

AC:

871

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.000818

EpiControl

AF:

0.000771

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.75

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.00079

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.75

FATHMM_MKL

Benign

0.096

LIST_S2

Benign

0.080

MetaRNN

Benign

0.0027

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.11

PhyloP100

-1.3

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.12

REVEL

Benign

0.043

Sift

Uncertain

0.024

Sift4G

Benign

0.12

Polyphen

0.0

Vest4

0.16

MVP

0.33

ClinPred

0.0026

GERP RS

2.0

Varity_R

0.082

gMVP

0.078

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

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5-141122501-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over