1-45012132-T-G

Variant summary

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

The ENST00000652165.1(UROD):c.-136+47T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00725 in 1,316,932 control chromosomes in the GnomAD database, including 487 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.034 (264 hom., cov: 32)
  • Exomes 𝑓: 0.0038 (223 hom.)
• Consequence: UROD ENST00000652165.1 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.61

Genes affected

UROD (HGNC:12591): (uroporphyrinogen decarboxylase) This gene encodes an enzyme in the heme biosynthetic pathway. This enzyme is responsible for catalyzing the conversion of uroporphyrinogen to coproporphyrinogen through the removal of four carboxymethyl side chains. Mutations and deficiency in this enzyme are known to cause familial porphyria cutanea tarda and hepatoerythropoetic porphyria.[provided by RefSeq, Aug 2010]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 1-45012132-T-G is Benign according to our data. Variant chr1-45012132-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 368874.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UROD	ENST00000650713.1	c.-86+47T>G		intron_variant
UROD	ENST00000652165.1	c.-136+47T>G		intron_variant
UROD	ENST00000651476.1			upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.0336 AC: 5101 AN: 152040 Hom.: 262 Cov.: 32

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0129

Gnomad ASJ AF: 0.000289

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000515

Gnomad OTH AF: 0.0259

GnomAD3 exomes AF: 0.00857 AC: 2010 AN: 234542 Hom.: 118 AF XY: 0.00621 AC XY: 790 AN XY: 127114

Gnomad AFR exome AF: 0.119

Gnomad AMR exome AF: 0.00633

Gnomad ASJ exome AF: 0.000104

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000237

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000576

Gnomad OTH exome AF: 0.00429

GnomAD4 exome AF: 0.00380 AC: 4430 AN: 1164774 Hom.: 223 Cov.: 16 AF XY: 0.00327 AC XY: 1934 AN XY: 592316

Gnomad4 AFR exome AF: 0.119

Gnomad4 AMR exome AF: 0.00698

Gnomad4 ASJ exome AF: 0.0000415

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000189

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000389

Gnomad4 OTH exome AF: 0.00908

GnomAD4 genome AF: 0.0336 AC: 5114 AN: 152158 Hom.: 264 Cov.: 32 AF XY: 0.0324 AC XY: 2411 AN XY: 74406

Gnomad4 AFR AF: 0.116

Gnomad4 AMR AF: 0.0129

Gnomad4 ASJ AF: 0.000289

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000515

Gnomad4 OTH AF: 0.0256

Alfa AF: 0.0152 Hom.: 31

Bravo AF: 0.0381

Asia WGS AF: 0.00549 AC: 20 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Porphyria cutanea tarda Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	0.091
Dann	Benign	0.35

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7536892; hg19: chr1-45477804;