rs4142274

Positions:

• chr13-67062637-G-T

Variant summary

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

The NM_203487.3(PCDH9):​c.3037-159032C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 152,074 control chromosomes in the GnomAD database, including 4,170 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 0.22 (4170 hom., cov: 32)
• Consequence: PCDH9 NM_203487.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.169

Genes affected

PCDH9 (HGNC:8661): (protocadherin 9) This gene encodes a member of the protocadherin family, and cadherin superfamily, of transmembrane proteins containing cadherin domains. These proteins mediate cell adhesion in neural tissues in the presence of calcium. The encoded protein may be involved in signaling at neuronal synaptic junctions. Sharing a characteristic with other protocadherin genes, this gene has a notably large exon that encodes multiple cadherin domains and a transmembrane region. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Nov 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.546 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCDH9	NM_203487.3	c.3037-159032C>A		intron_variant		ENST00000377865.7	NP_982354.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCDH9	ENST00000377865.7	c.3037-159032C>A		intron_variant		1	NM_203487.3	ENSP00000367096
PCDH9	ENST00000456367.5	c.3037-159032C>A		intron_variant		1		ENSP00000401699
PCDH9	ENST00000544246.5	c.3036+162768C>A		intron_variant		1		ENSP00000442186	P1

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33568 AN: 151956 Hom.: 4160 Cov.: 32

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.563

Gnomad SAS AF: 0.273

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.245

Gnomad OTH AF: 0.209

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

GnomAD4 genome AF: 0.221 AC: 33589 AN: 152074 Hom.: 4170 Cov.: 32 AF XY: 0.222 AC XY: 16511 AN XY: 74342

Gnomad4 AFR AF: 0.158

Gnomad4 AMR AF: 0.171

Gnomad4 ASJ AF: 0.234

Gnomad4 EAS AF: 0.563

Gnomad4 SAS AF: 0.273

Gnomad4 FIN AF: 0.200

Gnomad4 NFE AF: 0.245

Gnomad4 OTH AF: 0.214

Alfa AF: 0.240 Hom.: 9420

Bravo AF: 0.216

Asia WGS AF: 0.361 AC: 1251 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.6
DANN	Benign	0.70

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: rs4142274; hg19: chr13-67636769;