rs11244664

Variant names:

• chr10-125815820-G-A
• rs11244664
• NM_000375.3:c.147+357C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-125815820-G-A
• chr10-125815820-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000375.3(UROS):​c.147+357C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 152,070 control chromosomes in the GnomAD database, including 12,885 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 (12885 hom., cov: 32)
• Consequence: UROS NM_000375.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.329
• Publications: 16 publications found

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]

UROS Gene-Disease associations (from GenCC):

• cutaneous porphyria

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P, Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• 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 rank	MANE	Protein	UniProt
UROS	NM_000375.3	c.147+357C>T		intron_variant	Intron 3 of 9	ENST00000368797.10	NP_000366.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UROS	ENST00000368797.10	c.147+357C>T		intron_variant	Intron 3 of 9	1	NM_000375.3	ENSP00000357787.4

Frequencies

GnomAD3 genomes AF: 0.405 AC: 61610 AN: 151952 Hom.: 12871 Cov.: 32

Gnomad AFR AF: 0.349

Gnomad AMI AF: 0.538

Gnomad AMR AF: 0.325

Gnomad ASJ AF: 0.389

Gnomad EAS AF: 0.292

Gnomad SAS AF: 0.410

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.462

Gnomad OTH AF: 0.411

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

GnomAD4 genome AF: 0.405 AC: 61653 AN: 152070 Hom.: 12885 Cov.: 32 AF XY: 0.401 AC XY: 29795 AN XY: 74336

African (AFR) AF: 0.349 AC: 14457 AN: 41466

American (AMR) AF: 0.324 AC: 4951 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.389 AC: 1350 AN: 3470

East Asian (EAS) AF: 0.292 AC: 1511 AN: 5170

South Asian (SAS) AF: 0.410 AC: 1979 AN: 4822

European-Finnish (FIN) AF: 0.429 AC: 4544 AN: 10580

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.462 AC: 31406 AN: 67978

Other (OTH) AF: 0.414 AC: 875 AN: 2112

Alfa AF: 0.401 Hom.: 5071

Bravo AF: 0.392

Asia WGS AF: 0.362 AC: 1260 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.84
DANN	Benign	0.58
PhyloP100		-0.33
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11244664; hg19: chr10-127504389;