rs2281955

Positions:

• chr10-125796048-C-G
• chr10-125796048-C-T

Variant summary

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

The NM_000375.3(UROS):​c.561+55G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.447 in 1,534,740 control chromosomes in the GnomAD database, including 155,769 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.43 (14212 hom., cov: 32)
  • Exomes 𝑓: 0.45 (141557 hom.)
• Consequence: UROS NM_000375.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.63

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 10-125796048-C-G is Benign according to our data. Variant chr10-125796048-C-G is described in ClinVar as [Benign]. Clinvar id is 1257905.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.459 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UROS	NM_000375.3	c.561+55G>C		intron_variant		ENST00000368797.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UROS	ENST00000368797.10	c.561+55G>C		intron_variant		1	NM_000375.3	P1

Frequencies

GnomAD3 genomes AF: 0.429 AC: 65181 AN: 151894 Hom.: 14196 Cov.: 32

Gnomad AFR AF: 0.427

Gnomad AMI AF: 0.538

Gnomad AMR AF: 0.334

Gnomad ASJ AF: 0.390

Gnomad EAS AF: 0.294

Gnomad SAS AF: 0.424

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.463

Gnomad OTH AF: 0.428

GnomAD4 exome AF: 0.449 AC: 620885 AN: 1382728 Hom.: 141557 AF XY: 0.449 AC XY: 310876 AN XY: 692628

Gnomad4 AFR exome AF: 0.425

Gnomad4 AMR exome AF: 0.248

Gnomad4 ASJ exome AF: 0.390

Gnomad4 EAS exome AF: 0.306

Gnomad4 SAS exome AF: 0.424

Gnomad4 FIN exome AF: 0.427

Gnomad4 NFE exome AF: 0.470

Gnomad4 OTH exome AF: 0.429

GnomAD4 genome AF: 0.429 AC: 65227 AN: 152012 Hom.: 14212 Cov.: 32 AF XY: 0.423 AC XY: 31452 AN XY: 74286

Gnomad4 AFR AF: 0.427

Gnomad4 AMR AF: 0.334

Gnomad4 ASJ AF: 0.390

Gnomad4 EAS AF: 0.294

Gnomad4 SAS AF: 0.425

Gnomad4 FIN AF: 0.429

Gnomad4 NFE AF: 0.463

Gnomad4 OTH AF: 0.430

Alfa AF: 0.447 Hom.: 1813

Bravo AF: 0.419

Asia WGS AF: 0.372 AC: 1294 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

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.23
DANN	Benign	0.50
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2281955; hg19: chr10-127484617; COSMIC: COSV64229854; COSMIC: COSV64229854;