chr5-141248709-A-G

Position:

• chr5-141248709-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018935.4(PCDHB15):​c.*767A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0459 in 152,188 control chromosomes in the GnomAD database, including 177 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 0.046 (177 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PCDHB15 NM_018935.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.124

Genes affected

PCDHB15 (HGNC:8686): (protocadherin beta 15) 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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0567 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCDHB15	NM_018935.4	c.*767A>G		3_prime_UTR_variant	1/1	ENST00000231173.6	NP_061758.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCDHB15	ENST00000231173.6	c.*767A>G		3_prime_UTR_variant	1/1	6	NM_018935.4	ENSP00000231173.3

Frequencies

GnomAD3 genomes AF: 0.0459 AC: 6982 AN: 152070 Hom.: 177 Cov.: 32

Gnomad AFR AF: 0.0327

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.0392

Gnomad ASJ AF: 0.0571

Gnomad EAS AF: 0.000581

Gnomad SAS AF: 0.0168

Gnomad FIN AF: 0.0578

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0582

Gnomad OTH AF: 0.0445

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 4

Gnomad4 ASJ exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0459 AC: 6986 AN: 152188 Hom.: 177 Cov.: 32 AF XY: 0.0447 AC XY: 3325 AN XY: 74400

Gnomad4 AFR AF: 0.0327

Gnomad4 AMR AF: 0.0391

Gnomad4 ASJ AF: 0.0571

Gnomad4 EAS AF: 0.000582

Gnomad4 SAS AF: 0.0174

Gnomad4 FIN AF: 0.0578

Gnomad4 NFE AF: 0.0583

Gnomad4 OTH AF: 0.0440

Alfa AF: 0.0523 Hom.: 159

Bravo AF: 0.0433

Asia WGS AF: 0.00924 AC: 33 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.2
DANN	Benign	0.38

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: rs17642669; hg19: chr5-140628277;