chrX-100314162-A-G

Position:

• chrX-100314162-A-G

Variant summary

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

The NM_001184880.2(PCDH19):​c.2849-17287T>C variant causes a intron change. The variant allele was found at a frequency of 0.329 in 110,922 control chromosomes in the GnomAD database, including 5,371 homozygotes. There are 11,094 hemizygotes in GnomAD. 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 0.33 (5371 hom., 11094 hem., cov: 23)
• Consequence: PCDH19 NM_001184880.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.34

Genes affected

PCDH19 (HGNC:14270): (protocadherin 19) The protein encoded by this gene is a member of the delta-2 protocadherin subclass of the cadherin superfamily. The encoded protein is thought to be a calcium-dependent cell-adhesion protein that is primarily expressed in the brain. Mutations in this gene on human chromosome X are associated with sporadic infantile epileptic encephalopathy and to a female-restricted form of epilepsy (EFMR; also known as PCDH19RE). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.628 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCDH19	NM_001184880.2	c.2849-17287T>C		intron_variant		ENST00000373034.8	NP_001171809.1
PCDH19	NM_001105243.2	c.2708-17287T>C		intron_variant			NP_001098713.1
PCDH19	NM_020766.3	c.2705-17287T>C		intron_variant			NP_065817.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCDH19	ENST00000373034.8	c.2849-17287T>C		intron_variant		1	NM_001184880.2	ENSP00000362125.4
PCDH19	ENST00000255531.8	c.2708-17287T>C		intron_variant		1		ENSP00000255531.7
PCDH19	ENST00000420881.6	c.2705-17287T>C		intron_variant		1		ENSP00000400327.2

Frequencies

GnomAD3 genomes AF: 0.329 AC: 36511 AN: 110871 Hom.: 5378 Cov.: 23 AF XY: 0.335 AC XY: 11089 AN XY: 33133

Gnomad AFR AF: 0.0668

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.313

Gnomad ASJ AF: 0.401

Gnomad EAS AF: 0.651

Gnomad SAS AF: 0.552

Gnomad FIN AF: 0.507

Gnomad MID AF: 0.359

Gnomad NFE AF: 0.426

Gnomad OTH AF: 0.355

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

GnomAD4 genome AF: 0.329 AC: 36499 AN: 110922 Hom.: 5371 Cov.: 23 AF XY: 0.334 AC XY: 11094 AN XY: 33194

Gnomad4 AFR AF: 0.0667

Gnomad4 AMR AF: 0.313

Gnomad4 ASJ AF: 0.401

Gnomad4 EAS AF: 0.650

Gnomad4 SAS AF: 0.551

Gnomad4 FIN AF: 0.507

Gnomad4 NFE AF: 0.426

Gnomad4 OTH AF: 0.357

Alfa AF: 0.410 Hom.: 10050

Bravo AF: 0.306

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	19
DANN	Benign	0.71

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: rs5920818; hg19: chrX-99569160;