rs6730083

Positions:

• chr2-72888868-G-A
• chr2-72888868-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003124.5(SPR):​c.595+264G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.836 in 152,200 control chromosomes in the GnomAD database, including 54,537 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.84 (54537 hom., cov: 32)
• Consequence: SPR NM_003124.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.297

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 2-72888868-G-A is Benign according to our data. Variant chr2-72888868-G-A is described in ClinVar as [Benign]. Clinvar id is 1280180.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.97 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPR	NM_003124.5	c.595+264G>A		intron_variant		ENST00000234454.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPR	ENST00000234454.6	c.595+264G>A		intron_variant		1	NM_003124.5	P1
SPR	ENST00000498749.1	n.540+264G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.837 AC: 127256 AN: 152082 Hom.: 54529 Cov.: 32

Gnomad AFR AF: 0.634

Gnomad AMI AF: 0.876

Gnomad AMR AF: 0.895

Gnomad ASJ AF: 0.936

Gnomad EAS AF: 0.992

Gnomad SAS AF: 0.936

Gnomad FIN AF: 0.947

Gnomad MID AF: 0.908

Gnomad NFE AF: 0.904

Gnomad OTH AF: 0.855

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

GnomAD4 genome AF: 0.836 AC: 127290 AN: 152200 Hom.: 54537 Cov.: 32 AF XY: 0.842 AC XY: 62654 AN XY: 74420

Gnomad4 AFR AF: 0.633

Gnomad4 AMR AF: 0.895

Gnomad4 ASJ AF: 0.936

Gnomad4 EAS AF: 0.992

Gnomad4 SAS AF: 0.937

Gnomad4 FIN AF: 0.947

Gnomad4 NFE AF: 0.904

Gnomad4 OTH AF: 0.851

Alfa AF: 0.866 Hom.: 7193

Bravo AF: 0.822

Asia WGS AF: 0.924 AC: 3215 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.7
DANN	Benign	0.73

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: rs6730083; hg19: chr2-73115997;