rs2281956

chr10-125795974-G-C

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+129C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 832,988 control chromosomes in the GnomAD database, including 79,252 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.43 (14207 hom., cov: 32)
  • Exomes 𝑓: 0.43 (65045 hom.)
• Consequence: UROS NM_000375.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0790

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=-0.84).
• BP6: Variant 10-125795974-G-C is Benign according to our data. Variant chr10-125795974-G-C is described in ClinVar as [Benign]. Clinvar id is 1265038.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+129C>G		intron_variant		ENST00000368797.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UROS	ENST00000368797.10	c.561+129C>G		intron_variant		1	NM_000375.3	P1

Frequencies

GnomAD3 genomes AF: 0.429 AC: 65134 AN: 151886 Hom.: 14192 Cov.: 32

Gnomad AFR AF: 0.429

Gnomad AMI AF: 0.538

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.389

Gnomad EAS AF: 0.290

Gnomad SAS AF: 0.414

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.463

Gnomad OTH AF: 0.425

GnomAD4 exome AF: 0.431 AC: 293678 AN: 680984 Hom.: 65045 AF XY: 0.432 AC XY: 157418 AN XY: 364206

Gnomad4 AFR exome AF: 0.425

Gnomad4 AMR exome AF: 0.246

Gnomad4 ASJ exome AF: 0.388

Gnomad4 EAS exome AF: 0.313

Gnomad4 SAS exome AF: 0.414

Gnomad4 FIN exome AF: 0.424

Gnomad4 NFE exome AF: 0.469

Gnomad4 OTH exome AF: 0.421

GnomAD4 genome AF: 0.429 AC: 65180 AN: 152004 Hom.: 14207 Cov.: 32 AF XY: 0.423 AC XY: 31414 AN XY: 74284

Gnomad4 AFR AF: 0.429

Gnomad4 AMR AF: 0.332

Gnomad4 ASJ AF: 0.389

Gnomad4 EAS AF: 0.290

Gnomad4 SAS AF: 0.414

Gnomad4 FIN AF: 0.429

Gnomad4 NFE AF: 0.463

Gnomad4 OTH AF: 0.428

Alfa AF: 0.456 Hom.: 1929

Bravo AF: 0.420

Asia WGS AF: 0.367 AC: 1280 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	-0.84
Cadd	Benign	2.2
Dann	Benign	0.82
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: rs2281956; hg19: chr10-127484543; COSMIC: COSV64229824; COSMIC: COSV64229824;