rs10901450

Positions:

• chr10-125820725-G-C

Variant summary

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

The NM_000375.3(UROS):​c.-27+2304C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 152,068 control chromosomes in the GnomAD database, including 13,162 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 0.41 (13162 hom., cov: 32)
• Consequence: UROS NM_000375.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0430

Genes affected

UROS (HGNC:12592): (uroporphyrinogen III synthase) The protein encoded by this gene catalyzes the fourth step of porphyrin biosynthesis in the heme biosynthetic pathway. Defects in this gene cause congenital erythropoietic porphyria (Gunther's disease). [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.462 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UROS	NM_000375.3	c.-27+2304C>G		intron_variant		ENST00000368797.10	NP_000366.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UROS	ENST00000368797.10	c.-27+2304C>G		intron_variant		1	NM_000375.3	ENSP00000357787	P1

Frequencies

GnomAD3 genomes AF: 0.410 AC: 62318 AN: 151950 Hom.: 13148 Cov.: 32

Gnomad AFR AF: 0.358

Gnomad AMI AF: 0.538

Gnomad AMR AF: 0.325

Gnomad ASJ AF: 0.390

Gnomad EAS AF: 0.292

Gnomad SAS AF: 0.414

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.466

Gnomad OTH AF: 0.415

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

GnomAD4 genome AF: 0.410 AC: 62362 AN: 152068 Hom.: 13162 Cov.: 32 AF XY: 0.405 AC XY: 30136 AN XY: 74342

Gnomad4 AFR AF: 0.358

Gnomad4 AMR AF: 0.325

Gnomad4 ASJ AF: 0.390

Gnomad4 EAS AF: 0.292

Gnomad4 SAS AF: 0.414

Gnomad4 FIN AF: 0.430

Gnomad4 NFE AF: 0.466

Gnomad4 OTH AF: 0.418

Alfa AF: 0.449 Hom.: 2120

Bravo AF: 0.397

Asia WGS AF: 0.366 AC: 1273 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.4
DANN	Benign	0.58

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: rs10901450; hg19: chr10-127509294;