rs12218438

chr10-70886580-C-T

Variant summary

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

The NM_000281.4(PCBD1):c.4-651G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0726 in 152,274 control chromosomes in the GnomAD database, including 640 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 0.073 (640 hom., cov: 33)
• Consequence: PCBD1 NM_000281.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0780

Genes affected

PCBD1 (HGNC:8646): (pterin-4 alpha-carbinolamine dehydratase 1) This gene encodes a member of the pterin-4-alpha-carbinolamine dehydratase family. The encoded protein has been identified as a moonlighting protein based on its ability to perform mechanistically distinct functions. The encoded protein functions as both a dehydratase involved in tetrahydrobiopterin biosynthesis, and as a cofactor for HNF1A-dependent transcription. A deficiency of this enzyme leads to hyperphenylalaninemia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

SGPL1 (HGNC:10817): (sphingosine-1-phosphate lyase 1) Enables sphinganine-1-phosphate aldolase activity. Involved in apoptotic signaling pathway; fatty acid metabolic process; and sphingolipid metabolic process. Located in endoplasmic reticulum. Implicated in nephrotic syndrome type 14. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCBD1	NM_000281.4	c.4-651G>A		intron_variant		ENST00000299299.4
PCBD1	NM_001289797.2	c.-144-651G>A		intron_variant
PCBD1	NM_001323004.2	c.4-651G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCBD1	ENST00000299299.4	c.4-651G>A		intron_variant		1	NM_000281.4	P1
SGPL1	ENST00000697988.1	c.571-7179C>T		intron_variant
PCBD1	ENST00000493228.1	n.403-651G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0726 AC: 11053 AN: 152156 Hom.: 642 Cov.: 33

Gnomad AFR AF: 0.0189

Gnomad AMI AF: 0.0363

Gnomad AMR AF: 0.0930

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.301

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.0599

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.0800

Gnomad OTH AF: 0.0785

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

GnomAD4 genome AF: 0.0726 AC: 11052 AN: 152274 Hom.: 640 Cov.: 33 AF XY: 0.0743 AC XY: 5528 AN XY: 74448

Gnomad4 AFR AF: 0.0189

Gnomad4 AMR AF: 0.0932

Gnomad4 ASJ AF: 0.107

Gnomad4 EAS AF: 0.300

Gnomad4 SAS AF: 0.123

Gnomad4 FIN AF: 0.0599

Gnomad4 NFE AF: 0.0800

Gnomad4 OTH AF: 0.0791

Alfa AF: 0.0834 Hom.: 835

Bravo AF: 0.0746

Asia WGS AF: 0.230 AC: 797 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.23
Dann	Benign	0.72

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: rs12218438; hg19: chr10-72646337;