rs2149019

Positions:

• chr10-125794381-G-A

Variant summary

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

The NM_000375.3(UROS):​c.660+499C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 1,004,508 control chromosomes in the GnomAD database, including 105,303 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 (13091 hom., cov: 32)
  • Exomes 𝑓: 0.46 (92212 hom.)
• Consequence: UROS NM_000375.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0230

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=-0.6).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UROS	NM_000375.3	c.660+499C>T		intron_variant		ENST00000368797.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UROS	ENST00000368797.10	c.660+499C>T		intron_variant		1	NM_000375.3	P1

Frequencies

GnomAD3 genomes AF: 0.410 AC: 62285 AN: 151910 Hom.: 13083 Cov.: 32

Gnomad AFR AF: 0.363

Gnomad AMI AF: 0.537

Gnomad AMR AF: 0.327

Gnomad ASJ AF: 0.379

Gnomad EAS AF: 0.300

Gnomad SAS AF: 0.424

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.462

Gnomad OTH AF: 0.404

GnomAD4 exome AF: 0.464 AC: 395295 AN: 852480 Hom.: 92212 Cov.: 27 AF XY: 0.464 AC XY: 183347 AN XY: 395462

Gnomad4 AFR exome AF: 0.364

Gnomad4 AMR exome AF: 0.255

Gnomad4 ASJ exome AF: 0.380

Gnomad4 EAS exome AF: 0.274

Gnomad4 SAS exome AF: 0.417

Gnomad4 FIN exome AF: 0.398

Gnomad4 NFE exome AF: 0.471

Gnomad4 OTH exome AF: 0.439

GnomAD4 genome AF: 0.410 AC: 62319 AN: 152028 Hom.: 13091 Cov.: 32 AF XY: 0.405 AC XY: 30128 AN XY: 74310

Gnomad4 AFR AF: 0.362

Gnomad4 AMR AF: 0.326

Gnomad4 ASJ AF: 0.379

Gnomad4 EAS AF: 0.300

Gnomad4 SAS AF: 0.425

Gnomad4 FIN AF: 0.429

Gnomad4 NFE AF: 0.463

Gnomad4 OTH AF: 0.407

Alfa AF: 0.425 Hom.: 2193

Bravo AF: 0.398

Asia WGS AF: 0.370 AC: 1288 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	13
DANN	Benign	0.92

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs2149019; hg19: chr10-127482950;