rs2027515

chr10-125807263-T-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.394+150A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.758 in 714,674 control chromosomes in the GnomAD database, including 207,539 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.72 (40594 hom., cov: 32)
  • Exomes 𝑓: 0.77 (166945 hom.)
• Consequence: UROS NM_000375.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.94

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=-0.91).
• BP6: Variant 10-125807263-T-C is Benign according to our data. Variant chr10-125807263-T-C is described in ClinVar as [Benign]. Clinvar id is 1276252.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.785 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UROS	NM_000375.3	c.394+150A>G		intron_variant		ENST00000368797.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UROS	ENST00000368797.10	c.394+150A>G		intron_variant		1	NM_000375.3	P1

Frequencies

GnomAD3 genomes AF: 0.724 AC: 110081 AN: 151972 Hom.: 40574 Cov.: 32

Gnomad AFR AF: 0.617

Gnomad AMI AF: 0.809

Gnomad AMR AF: 0.623

Gnomad ASJ AF: 0.745

Gnomad EAS AF: 0.704

Gnomad SAS AF: 0.775

Gnomad FIN AF: 0.840

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.791

Gnomad OTH AF: 0.716

GnomAD4 exome AF: 0.767 AC: 431568 AN: 562584 Hom.: 166945 Cov.: 7 AF XY: 0.769 AC XY: 231603 AN XY: 301138

Gnomad4 AFR exome AF: 0.620

Gnomad4 AMR exome AF: 0.585

Gnomad4 ASJ exome AF: 0.751

Gnomad4 EAS exome AF: 0.681

Gnomad4 SAS exome AF: 0.775

Gnomad4 FIN exome AF: 0.846

Gnomad4 NFE exome AF: 0.792

Gnomad4 OTH exome AF: 0.749

GnomAD4 genome AF: 0.724 AC: 110150 AN: 152090 Hom.: 40594 Cov.: 32 AF XY: 0.726 AC XY: 53952 AN XY: 74360

Gnomad4 AFR AF: 0.617

Gnomad4 AMR AF: 0.623

Gnomad4 ASJ AF: 0.745

Gnomad4 EAS AF: 0.704

Gnomad4 SAS AF: 0.774

Gnomad4 FIN AF: 0.840

Gnomad4 NFE AF: 0.791

Gnomad4 OTH AF: 0.718

Alfa AF: 0.738 Hom.: 14801

Bravo AF: 0.702

Asia WGS AF: 0.731 AC: 2546 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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.051
Dann	Benign	0.46

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: rs2027515; hg19: chr10-127495832; COSMIC: COSV64223420;