X-24642466-T-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_004845.5(PCYT1B):c.117+4523A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.65 (16879 hom., 21739 hem., cov: 24)
  • Failed GnomAD Quality Control
• Consequence: PCYT1B NM_004845.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.710

Genes affected

PCYT1B (HGNC:8755): (phosphate cytidylyltransferase 1B, choline) The protein encoded by this gene belongs to the cytidylyltransferase family. It is involved in the regulation of phosphatidylcholine biosynthesis. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BS2: High Homozygotes in GnomAd at 16879 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCYT1B	NM_004845.5	c.117+4523A>G		intron_variant		ENST00000379144.7
PCYT1B	NM_001163264.2	c.64-23382A>G		intron_variant
PCYT1B	NM_001163265.2	c.117+4523A>G		intron_variant
PCYT1B	XM_017029977.2	c.-291-2005A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCYT1B	ENST00000379144.7	c.117+4523A>G		intron_variant		1	NM_004845.5	P1
PCYT1B	ENST00000356768.8	c.117+4523A>G		intron_variant		1
PCYT1B	ENST00000379145.5	c.64-23382A>G		intron_variant		1
PCYT1B	ENST00000496020.1	c.39+4523A>G		intron_variant, NMD_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.652 AC: 72522 AN: 111294 Hom.: 16879 Cov.: 24 AF XY: 0.647 AC XY: 21692 AN XY: 33504

Gnomad AFR AF: 0.780

Gnomad AMI AF: 0.369

Gnomad AMR AF: 0.687

Gnomad ASJ AF: 0.550

Gnomad EAS AF: 0.695

Gnomad SAS AF: 0.565

Gnomad FIN AF: 0.563

Gnomad MID AF: 0.542

Gnomad NFE AF: 0.592

Gnomad OTH AF: 0.645

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

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.652 AC: 72566 AN: 111347 Hom.: 16879 Cov.: 24 AF XY: 0.648 AC XY: 21739 AN XY: 33567

Gnomad4 AFR AF: 0.779

Gnomad4 AMR AF: 0.687

Gnomad4 ASJ AF: 0.550

Gnomad4 EAS AF: 0.695

Gnomad4 SAS AF: 0.566

Gnomad4 FIN AF: 0.563

Gnomad4 NFE AF: 0.592

Gnomad4 OTH AF: 0.642

Alfa AF: 0.610 Hom.: 5496

Bravo AF: 0.669

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.3
Dann	Benign	0.56

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: rs2214600; hg19: chrX-24660583;