rs12251135

Variant names:

• chr10-125806628-T-C
• rs12251135
• NM_000375.3:c.394+785A>G

Variant summary

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

The NM_000375.3(UROS):​c.394+785A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 152,216 control chromosomes in the GnomAD database, including 7,235 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 0.30 (7235 hom., cov: 33)
• Consequence: UROS NM_000375.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.272

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.399 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UROS	NM_000375.3	c.394+785A>G		intron_variant	Intron 6 of 9	ENST00000368797.10	NP_000366.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UROS	ENST00000368797.10	c.394+785A>G		intron_variant	Intron 6 of 9	1	NM_000375.3	ENSP00000357787.4

Frequencies

GnomAD3 genomes AF: 0.302 AC: 45934 AN: 152098 Hom.: 7236 Cov.: 33

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.271

Gnomad AMR AF: 0.290

Gnomad ASJ AF: 0.354

Gnomad EAS AF: 0.414

Gnomad SAS AF: 0.362

Gnomad FIN AF: 0.409

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.324

Gnomad OTH AF: 0.292

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.302 AC: 45955 AN: 152216 Hom.: 7235 Cov.: 33 AF XY: 0.309 AC XY: 22966 AN XY: 74422

Gnomad4 AFR AF: 0.218

Gnomad4 AMR AF: 0.290

Gnomad4 ASJ AF: 0.354

Gnomad4 EAS AF: 0.413

Gnomad4 SAS AF: 0.362

Gnomad4 FIN AF: 0.409

Gnomad4 NFE AF: 0.324

Gnomad4 OTH AF: 0.292

Alfa AF: 0.321 Hom.: 13344

Bravo AF: 0.291

Asia WGS AF: 0.363 AC: 1266 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.56
DANN	Benign	0.57

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: rs12251135; hg19: chr10-127495197;