rs827241

Positions:

• chr10-70887896-G-C
• chr10-70887896-G-T

Variant summary

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

The NM_000281.4(PCBD1):​c.3+635C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 152,346 control chromosomes in the GnomAD database, including 2,243 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 0.16 (2237 hom., cov: 32)
  • Exomes 𝑓: 0.20 (6 hom.)
• Consequence: PCBD1 NM_000281.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.326

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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCBD1	NM_000281.4	c.3+635C>G		intron_variant		ENST00000299299.4	NP_000272.1
PCBD1	NM_001323004.2	c.3+635C>G		intron_variant			NP_001309933.1
PCBD1	NM_001289797.2			upstream_gene_variant			NP_001276726.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCBD1	ENST00000299299.4	c.3+635C>G		intron_variant		1	NM_000281.4	ENSP00000299299	P1
SGPL1	ENST00000697988.1	c.571-5863G>C		intron_variant				ENSP00000513492
PCBD1	ENST00000493228.1	n.359C>G		non_coding_transcript_exon_variant	1/4	2

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24700 AN: 151970 Hom.: 2241 Cov.: 32

Gnomad AFR AF: 0.0823

Gnomad AMI AF: 0.223

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.0755

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.185

GnomAD4 exome AF: 0.202 AC: 52 AN: 258 Hom.: 6 Cov.: 0 AF XY: 0.184 AC XY: 36 AN XY: 196

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.125

Gnomad4 SAS exome AF: 0.100

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.209

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.162 AC: 24690 AN: 152088 Hom.: 2237 Cov.: 32 AF XY: 0.163 AC XY: 12110 AN XY: 74344

Gnomad4 AFR AF: 0.0821

Gnomad4 AMR AF: 0.190

Gnomad4 ASJ AF: 0.140

Gnomad4 EAS AF: 0.0755

Gnomad4 SAS AF: 0.117

Gnomad4 FIN AF: 0.249

Gnomad4 NFE AF: 0.201

Gnomad4 OTH AF: 0.183

Alfa AF: 0.0997 Hom.: 135

Bravo AF: 0.160

Asia WGS AF: 0.0830 AC: 287 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	11
DANN	Benign	0.36

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: rs827241; hg19: chr10-72647653;