5-141867081-T-C

Variant names:

• chr5-141867081-T-C
• rs10063472
• NM_032420.5:c.903+1488A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032420.5(PCDH1):​c.903+1488A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.804 in 152,148 control chromosomes in the GnomAD database, including 49,207 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 0.80 (49207 hom., cov: 32)
• Consequence: PCDH1 NM_032420.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0700
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.812 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCDH1	NM_032420.5	c.903+1488A>G		intron_variant	Intron 2 of 4	ENST00000287008.8	NP_115796.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCDH1	ENST00000287008.8	c.903+1488A>G		intron_variant	Intron 2 of 4	5	NM_032420.5	ENSP00000287008.3

Frequencies

GnomAD3 genomes AF: 0.804 AC: 122201 AN: 152030 Hom.: 49154 Cov.: 32

Gnomad AFR AF: 0.781

Gnomad AMI AF: 0.846

Gnomad AMR AF: 0.817

Gnomad ASJ AF: 0.819

Gnomad EAS AF: 0.803

Gnomad SAS AF: 0.833

Gnomad FIN AF: 0.865

Gnomad MID AF: 0.816

Gnomad NFE AF: 0.803

Gnomad OTH AF: 0.783

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.804 AC: 122317 AN: 152148 Hom.: 49207 Cov.: 32 AF XY: 0.807 AC XY: 60002 AN XY: 74374

African (AFR) AF: 0.781 AC: 32414 AN: 41500

American (AMR) AF: 0.817 AC: 12491 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.819 AC: 2841 AN: 3470

East Asian (EAS) AF: 0.802 AC: 4155 AN: 5180

South Asian (SAS) AF: 0.833 AC: 4010 AN: 4812

European-Finnish (FIN) AF: 0.865 AC: 9172 AN: 10602

Middle Eastern (MID) AF: 0.823 AC: 242 AN: 294

European-Non Finnish (NFE) AF: 0.803 AC: 54569 AN: 67984

Other (OTH) AF: 0.785 AC: 1651 AN: 2102

Alfa AF: 0.796 Hom.: 87382

Bravo AF: 0.795

Asia WGS AF: 0.821 AC: 2852 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	4.3
DANN	Benign	0.52
PhyloP100		0.070
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: rs10063472; hg19: chr5-141246646; COSMIC: COSV54612466; COSMIC: COSV54612466;