dbSNP rs3740179: UROS:c.562-26C>T (chr10-125795004-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000375.3(UROS):c.562-26C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.447 in 1,589,188 control chromosomes in the GnomAD database, including 161,003 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.43 ( 14234 hom., cov: 32)

Exomes 𝑓: 0.45 ( 146769 hom. )

Consequence

UROS
NM_000375.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.352

Publications

28 publications found

Variant links:

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: ClinGen, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P, Orphanet

UROS links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 10-125795004-G-A is Benign according to our data. Variant chr10-125795004-G-A is described in ClinVar as Benign. ClinVar VariationId is 1266364.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.459 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000375.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
UROS	NM_000375.3	MANE Select	c.562-26C>T	intron	N/A	NP_000366.1	A0A0S2Z4T8
UROS	NM_001324036.2		c.562-26C>T	intron	N/A	NP_001310965.1	A0A3B3ISM6
UROS	NM_001324037.2		c.481-26C>T	intron	N/A	NP_001310966.1	A0A3B3ITJ2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
UROS	ENST00000368797.10	TSL:1 MANE Select	c.562-26C>T	intron	N/A	ENSP00000357787.4	P10746
UROS	ENST00000368786.5	TSL:1	c.562-26C>T	intron	N/A	ENSP00000357775.1	P10746
UROS	ENST00000940865.1		c.661-26C>T	intron	N/A	ENSP00000610924.1

Frequencies

GnomAD3 genomes

AF:

0.429

AC:

65234

AN:

151958

Hom.:

14220

Cov.:

show subpopulations

Gnomad AFR

AF:

0.429

Gnomad AMI

AF:

0.541

Gnomad AMR

AF:

0.333

Gnomad ASJ

AF:

0.382

Gnomad EAS

AF:

0.300

Gnomad SAS

AF:

0.424

Gnomad FIN

AF:

0.429

Gnomad MID

AF:

0.310

Gnomad NFE

AF:

0.463

Gnomad OTH

AF:

0.424

GnomAD2 exomes

AF:

0.400

AC:

100478

AN:

250906

AF XY:

0.407

show subpopulations

Gnomad AFR exome

AF:

0.431

Gnomad AMR exome

AF:

0.239

Gnomad ASJ exome

AF:

0.374

Gnomad EAS exome

AF:

0.271

Gnomad FIN exome

AF:

0.419

Gnomad NFE exome

AF:

0.458

Gnomad OTH exome

AF:

0.400

GnomAD4 exome

AF:

0.449

AC:

644791

AN:

1437112

Hom.:

146769

Cov.:

AF XY:

0.448

AC XY:

321367

AN XY:

716656

show subpopulations

African (AFR)

AF:

0.425

AC:

13996

AN:

32916

American (AMR)

AF:

0.248

AC:

11073

AN:

44668

Ashkenazi Jewish (ASJ)

AF:

0.382

AC:

9920

AN:

25974

East Asian (EAS)

AF:

0.321

AC:

12669

AN:

39516

South Asian (SAS)

AF:

0.424

AC:

36297

AN:

85702

European-Finnish (FIN)

AF:

0.425

AC:

22677

AN:

53338

Middle Eastern (MID)

AF:

0.328

AC:

1876

AN:

5712

European-Non Finnish (NFE)

AF:

0.469

AC:

510711

AN:

1089674

Other (OTH)

AF:

0.429

AC:

25572

AN:

59612

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

16697

33393

50090

66786

83483

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14914

29828

44742

59656

74570

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.429

AC:

65279

AN:

152076

Hom.:

14234

Cov.:

AF XY:

0.423

AC XY:

31479

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.429

AC:

17787

AN:

41508

American (AMR)

AF:

0.332

AC:

5078

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.382

AC:

1326

AN:

3472

East Asian (EAS)

AF:

0.301

AC:

1552

AN:

5160

South Asian (SAS)

AF:

0.424

AC:

2042

AN:

4814

European-Finnish (FIN)

AF:

0.429

AC:

4534

AN:

10572

Middle Eastern (MID)

AF:

0.303

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.463

AC:

31480

AN:

67964

Other (OTH)

AF:

0.427

AC:

900

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1881

3761

5642

7522

9403

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

606

1212

1818

2424

3030

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.442

Hom.:

42963

Bravo

AF:

0.419

Asia WGS

AF:

0.372

AC:

1297

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Cutaneous porphyria (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.85

(source)

DANN

Benign

0.69

PhyloP100

-0.35

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over