Genetic Variant PCDHB16:p.Ala214Val (chr5-141183200-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

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

The NM_020957.4(PCDHB16):c.641C>T(p.Ala214Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00314 in 1,614,112 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0027 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0032 ( 26 hom. )

Consequence

PCDHB16
NM_020957.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.89

Variant links:

Genes affected

PCDHB16 (HGNC:14546): (protocadherin beta 16) 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]

PCDHB16 links:

PCDHB@ (HGNC:8679):

PCDHB@ links:

ENSG00000279068 (HGNC:):

ENSG00000279068 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=0.042093426).

BP6

Variant 5-141183200-C-T is Benign according to our data. Variant chr5-141183200-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2655820.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCDHB16	NM_020957.4 link	c.641C>T	p.Ala214Val	missense_variant	Exon 1 of 1	ENST00000609684.3	NP_066008.2	Q9NRJ7
PCDHB@		n.141183200C>T		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCDHB16	ENST00000609684.3 link	c.641C>T	p.Ala214Val	missense_variant	Exon 1 of 1	6	NM_020957.4	ENSP00000477314.1		Q9NRJ7

Frequencies

GnomAD3 genomes

AF:

0.00275

AC:

418

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000386

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.00548

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00311

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00497

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00292

AC:

735

AN:

251462

Hom.:

AF XY:

0.00285

AC XY:

387

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.000369

Gnomad AMR exome

AF:

0.000838

Gnomad ASJ exome

AF:

0.00506

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.00347

Gnomad NFE exome

AF:

0.00474

Gnomad OTH exome

AF:

0.00472

GnomAD4 exome

AF:

0.00318

AC:

4645

AN:

1461878

Hom.:

Cov.:

AF XY:

0.00318

AC XY:

2311

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.000299

Gnomad4 AMR exome

AF:

0.000850

Gnomad4 ASJ exome

AF:

0.00612

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000185

Gnomad4 FIN exome

AF:

0.00457

Gnomad4 NFE exome

AF:

0.00357

Gnomad4 OTH exome

AF:

0.00329

GnomAD4 genome

AF:

0.00275

AC:

418

AN:

152234

Hom.:

Cov.:

AF XY:

0.00241

AC XY:

179

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.000385

Gnomad4 AMR

AF:

0.000719

Gnomad4 ASJ

AF:

0.00548

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00311

Gnomad4 NFE

AF:

0.00497

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00374

Hom.:

Bravo

AF:

0.00234

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00419

AC:

ExAC

AF:

0.00326

AC:

396

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jan 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PCDHB16: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.094

BayesDel_noAF

Uncertain

0.10

CADD

Uncertain

DANN

Pathogenic

1.0

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Pathogenic

0.99

M_CAP

Benign

0.026

MetaRNN

Benign

0.042

MetaSVM

Benign

-0.41

PrimateAI

Uncertain

0.56

Sift4G

Pathogenic

0.0

Vest4

0.83

MVP

0.49

ClinPred

0.12

GERP RS

4.7

gMVP

0.31

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