NM_018933.4:c.1488G>T

Variant names:

• chr5-141215611-G-T
• rs2910330
• NM_018933.4:c.1488G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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:8679):

ENSG00000280029 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PCDHB13	NM_018933.4	c.1488G>T	p.Pro496Pro	synonymous_variant	Exon 1 of 1	ENST00000341948.6	NP_061756.1
PCDHB@		n.141215611G>T		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCDHB13	ENST00000341948.6	c.1488G>T	p.Pro496Pro	synonymous_variant	Exon 1 of 1	6	NM_018933.4	ENSP00000345491.4
ENSG00000280029	ENST00000624192.1	n.72+26062C>A		intron_variant	Intron 1 of 1	5
ENSG00000272154	ENST00000718175.1	n.71+20408C>A		intron_variant	Intron 1 of 1

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

GnomAD2 exomes AF: 0.145 AC: 36389 AN: 251340 AF XY: 0.150

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 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

African (AFR) AF: 0.109 AC: 3656 AN: 33450

American (AMR) AF: 0.0750 AC: 3353 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.160 AC: 4172 AN: 26136

East Asian (EAS) AF: 0.0949 AC: 3768 AN: 39700

South Asian (SAS) AF: 0.186 AC: 16009 AN: 86214

European-Finnish (FIN) AF: 0.186 AC: 9932 AN: 53406

Middle Eastern (MID) AF: 0.192 AC: 999 AN: 5204

European-Non Finnish (NFE) AF: 0.167 AC: 185929 AN: 1112008

Other (OTH) AF: 0.154 AC: 9274 AN: 60322

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

African (AFR) AF: 0.110 AC: 4584 AN: 41544

American (AMR) AF: 0.100 AC: 1533 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 561 AN: 3472

East Asian (EAS) AF: 0.0835 AC: 432 AN: 5172

South Asian (SAS) AF: 0.176 AC: 849 AN: 4824

European-Finnish (FIN) AF: 0.194 AC: 2059 AN: 10588

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.163 AC: 11098 AN: 67996

Other (OTH) AF: 0.139 AC: 293 AN: 2112

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
PhyloP100		-0.37
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2910330; hg19: chr5-140595183; COSMIC: COSV108050348; COSMIC: COSV108050348;