5-141215611-G-T

Position:

• chr5-141215611-G-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_018933.4(PCDHB13):​c.1488G>T​(p.Pro496Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 1,613,374 control chromosomes in the GnomAD database, including 21,477 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.14 (1628 hom., cov: 33)
  • Exomes 𝑓: 0.16 (19849 hom.)
• Consequence: PCDHB13 NM_018933.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.370

Genes affected

PCDHB13 (HGNC:8684): (protocadherin beta 13) 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]

PCDHB@ (HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP7: Synonymous conserved (PhyloP=-0.37 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCDHB13	NM_018933.4	c.1488G>T	p.Pro496Pro	synonymous_variant	1/1	ENST00000341948.6	NP_061756.1
PCDHB@		n.141215611G>T		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCDHB13	ENST00000341948.6	c.1488G>T	p.Pro496Pro	synonymous_variant	1/1	6	NM_018933.4	ENSP00000345491.4
ENSG00000280029	ENST00000624192.1	n.72+26062C>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21648 AN: 152092 Hom.: 1631 Cov.: 33

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.100

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.0833

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.139

GnomAD3 exomes AF: 0.145 AC: 36389 AN: 251340 Hom.: 2975 AF XY: 0.150 AC XY: 20393 AN XY: 135848

Gnomad AFR exome AF: 0.112

Gnomad AMR exome AF: 0.0709

Gnomad ASJ exome AF: 0.161

Gnomad EAS exome AF: 0.0831

Gnomad SAS exome AF: 0.185

Gnomad FIN exome AF: 0.188

Gnomad NFE exome AF: 0.161

Gnomad OTH exome AF: 0.149

GnomAD4 exome AF: 0.162 AC: 237092 AN: 1461162 Hom.: 19849 Cov.: 154 AF XY: 0.163 AC XY: 118472 AN XY: 726892

Gnomad4 AFR exome AF: 0.109

Gnomad4 AMR exome AF: 0.0750

Gnomad4 ASJ exome AF: 0.160

Gnomad4 EAS exome AF: 0.0949

Gnomad4 SAS exome AF: 0.186

Gnomad4 FIN exome AF: 0.186

Gnomad4 NFE exome AF: 0.167

Gnomad4 OTH exome AF: 0.154

GnomAD4 genome AF: 0.142 AC: 21648 AN: 152212 Hom.: 1628 Cov.: 33 AF XY: 0.144 AC XY: 10681 AN XY: 74416

Gnomad4 AFR AF: 0.110

Gnomad4 AMR AF: 0.100

Gnomad4 ASJ AF: 0.162

Gnomad4 EAS AF: 0.0835

Gnomad4 SAS AF: 0.176

Gnomad4 FIN AF: 0.194

Gnomad4 NFE AF: 0.163

Gnomad4 OTH AF: 0.139

Alfa AF: 0.122 Hom.: 395

Bravo AF: 0.132

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.5
DANN	Benign	0.86

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

Other links and lift over

dbSNP: rs2910330; hg19: chr5-140595183;