5-141863068-C-G

Variant summary

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

The ENST00000394536.4(PCDH1):c.*80G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 1,364,656 control chromosomes in the GnomAD database, including 31,231 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 0.18 (2610 hom., cov: 31)
  • Exomes 𝑓: 0.21 (28621 hom.)
• Consequence: PCDH1 ENST00000394536.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0300

Genes affected

PCDH1 (HGNC:8655): (protocadherin 1) This gene belongs to the protocadherin subfamily within the cadherin superfamily. The encoded protein is a membrane protein found at cell-cell boundaries. It is involved in neural cell adhesion, suggesting a possible role in neuronal development. The protein includes an extracelllular region, containing 7 cadherin-like domains, a transmembrane region and a C-terminal cytoplasmic region. Cells expressing the protein showed cell aggregation activity. Alternative splicing occurs in this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCDH1	NM_032420.5	c.3099+164G>C		intron_variant		ENST00000287008.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCDH1	ENST00000287008.8	c.3099+164G>C		intron_variant		5	NM_032420.5	P1

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26792 AN: 151922 Hom.: 2609 Cov.: 31

Gnomad AFR AF: 0.0862

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.168

GnomAD4 exome AF: 0.214 AC: 259510 AN: 1212616 Hom.: 28621 Cov.: 32 AF XY: 0.213 AC XY: 123643 AN XY: 579418

Gnomad4 AFR exome AF: 0.0793

Gnomad4 AMR exome AF: 0.222

Gnomad4 ASJ exome AF: 0.111

Gnomad4 EAS exome AF: 0.191

Gnomad4 SAS exome AF: 0.122

Gnomad4 FIN exome AF: 0.224

Gnomad4 NFE exome AF: 0.225

Gnomad4 OTH exome AF: 0.191

GnomAD4 genome AF: 0.176 AC: 26795 AN: 152040 Hom.: 2610 Cov.: 31 AF XY: 0.175 AC XY: 13027 AN XY: 74284

Gnomad4 AFR AF: 0.0862

Gnomad4 AMR AF: 0.194

Gnomad4 ASJ AF: 0.114

Gnomad4 EAS AF: 0.181

Gnomad4 SAS AF: 0.122

Gnomad4 FIN AF: 0.231

Gnomad4 NFE AF: 0.226

Gnomad4 OTH AF: 0.167

Alfa AF: 0.102 Hom.: 174

Bravo AF: 0.170

Asia WGS AF: 0.126 AC: 439 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	2.7
Dann	Benign	0.79

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: rs14359; hg19: chr5-141242633; COSMIC: COSV54613383; COSMIC: COSV54613383;