dbSNP rs1876487: SPR:c.-210A>C (chr2-72887223-A-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003124.5(SPR):c.-210A>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.654 in 462,886 control chromosomes in the GnomAD database, including 107,537 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.55 ( 28196 hom., cov: 33)

Exomes 𝑓: 0.70 ( 79341 hom. )

Consequence

SPR
NM_003124.5 upstream_gene

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -5.97

Variant links:

Genes affected

SPR (HGNC:11257): (sepiapterin reductase) This gene encodes an aldo-keto reductase that catalyzes the NADPH-dependent reduction of pteridine derivatives and is important in the biosynthesis of tetrahydrobiopterin (BH4). Mutations in this gene result in DOPA-responsive dystonia due to sepiaterin reductase deficiency. A pseudogene has been identified on chromosome 1. [provided by RefSeq, Jul 2008]

SPR links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 2-72887223-A-C is Benign according to our data. Variant chr2-72887223-A-C is described in ClinVar as [Benign]. Clinvar id is 1167479.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.912 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPR	NM_003124.5 link	c.-210A>C		upstream_gene_variant		ENST00000234454.6	NP_003115.1	P35270

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPR	ENST00000234454.6 link	c.-210A>C		upstream_gene_variant		1	NM_003124.5	ENSP00000234454.5		P35270
SPR	ENST00000498749.1 link	n.-159A>C		upstream_gene_variant		3		ENSP00000519026.1

Frequencies

GnomAD3 genomes

AF:

0.552

AC:

83872

AN:

151992

Hom.:

28209

Cov.:

show subpopulations

Gnomad AFR

AF:

0.149

Gnomad AMI

AF:

0.630

Gnomad AMR

AF:

0.590

Gnomad ASJ

AF:

0.763

Gnomad EAS

AF:

0.934

Gnomad SAS

AF:

0.851

Gnomad FIN

AF:

0.730

Gnomad MID

AF:

0.741

Gnomad NFE

AF:

0.697

Gnomad OTH

AF:

0.587

GnomAD4 exome

AF:

0.704

AC:

218778

AN:

310778

Hom.:

79341

AF XY:

0.709

AC XY:

112273

AN XY:

158430

show subpopulations

Gnomad4 AFR exome

AF:

0.147

Gnomad4 AMR exome

AF:

0.607

Gnomad4 ASJ exome

AF:

0.760

Gnomad4 EAS exome

AF:

0.932

Gnomad4 SAS exome

AF:

0.839

Gnomad4 FIN exome

AF:

0.717

Gnomad4 NFE exome

AF:

0.696

Gnomad4 OTH exome

AF:

0.674

GnomAD4 genome

AF:

0.551

AC:

83861

AN:

152108

Hom.:

28196

Cov.:

AF XY:

0.562

AC XY:

41778

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.149

Gnomad4 AMR

AF:

0.590

Gnomad4 ASJ

AF:

0.763

Gnomad4 EAS

AF:

0.934

Gnomad4 SAS

AF:

0.853

Gnomad4 FIN

AF:

0.730

Gnomad4 NFE

AF:

0.697

Gnomad4 OTH

AF:

0.586

Alfa

AF:

0.572

Hom.:

4877

Bravo

AF:

0.521

Asia WGS

AF:

0.820

AC:

2851

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 26, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 19415819) -

Dystonic disorder

Benign:1

Jan 23, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.54

DANN

Benign

0.43

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over