chr5-141858778-G-A

Position:

• chr5-141858778-G-A

Variant summary

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

The NM_032420.5(PCDH1):​c.3100-1307C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 152,142 control chromosomes in the GnomAD database, including 1,939 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 (1939 hom., cov: 31)
• Consequence: PCDH1 NM_032420.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.190

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCDH1	NM_032420.5	c.3100-1307C>T		intron_variant		ENST00000287008.8
PCDH1	XM_005268452.4	c.3148-1307C>T		intron_variant
PCDH1	XM_005268454.6	c.3148-1307C>T		intron_variant
PCDH1	XM_017009517.3	c.1963-1307C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCDH1	ENST00000287008.8	c.3100-1307C>T		intron_variant		5	NM_032420.5	P1
PCDH1	ENST00000503492.5	c.904-1307C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22034 AN: 152024 Hom.: 1939 Cov.: 31

Gnomad AFR AF: 0.0583

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.220

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.147

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.150

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

GnomAD4 genome AF: 0.145 AC: 22039 AN: 152142 Hom.: 1939 Cov.: 31 AF XY: 0.144 AC XY: 10738 AN XY: 74366

Gnomad4 AFR AF: 0.0585

Gnomad4 AMR AF: 0.195

Gnomad4 ASJ AF: 0.218

Gnomad4 EAS AF: 0.220

Gnomad4 SAS AF: 0.115

Gnomad4 FIN AF: 0.147

Gnomad4 NFE AF: 0.178

Gnomad4 OTH AF: 0.149

Alfa AF: 0.169 Hom.: 1547

Bravo AF: 0.148

Asia WGS AF: 0.175 AC: 608 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	8.8
DANN	Benign	0.50

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: rs11167761; hg19: chr5-141238343;