dbSNP rs10510149: UROS:c.394+175T>G (chr10-125807238-A-C) – 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.394+175T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.432 in 644,030 control chromosomes in the GnomAD database, including 61,360 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.42 ( 13837 hom., cov: 32)

Exomes 𝑓: 0.43 ( 47523 hom. )

Consequence

UROS
NM_000375.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.956

Publications

30 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: 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=-0.96).

BP6

Variant 10-125807238-A-C is Benign according to our data. Variant chr10-125807238-A-C is described in ClinVar as [Benign]. Clinvar id is 1273846.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.462 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UROS	NM_000375.3 link	c.394+175T>G		intron_variant	Intron 6 of 9	ENST00000368797.10	NP_000366.1	P10746A0A0S2Z4T8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UROS	ENST00000368797.10 link	c.394+175T>G		intron_variant	Intron 6 of 9	1	NM_000375.3	ENSP00000357787.4		P10746

Frequencies

GnomAD3 genomes

AF:

0.422

AC:

64184

AN:

151944

Hom.:

13821

Cov.:

show subpopulations

Gnomad AFR

AF:

0.398

Gnomad AMI

AF:

0.535

Gnomad AMR

AF:

0.332

Gnomad ASJ

AF:

0.390

Gnomad EAS

AF:

0.303

Gnomad SAS

AF:

0.424

Gnomad FIN

AF:

0.429

Gnomad MID

AF:

0.307

Gnomad NFE

AF:

0.466

Gnomad OTH

AF:

0.422

GnomAD4 exome

AF:

0.434

AC:

213704

AN:

491968

Hom.:

47523

Cov.:

AF XY:

0.436

AC XY:

114485

AN XY:

262772

show subpopulations

African (AFR)

AF:

0.395

AC:

5314

AN:

13452

American (AMR)

AF:

0.272

AC:

6509

AN:

23942

Ashkenazi Jewish (ASJ)

AF:

0.392

AC:

6098

AN:

15542

East Asian (EAS)

AF:

0.331

AC:

10282

AN:

31040

South Asian (SAS)

AF:

0.425

AC:

21366

AN:

50306

European-Finnish (FIN)

AF:

0.430

AC:

13584

AN:

31602

Middle Eastern (MID)

AF:

0.337

AC:

703

AN:

2084

European-Non Finnish (NFE)

AF:

0.467

AC:

138400

AN:

296462

Other (OTH)

AF:

0.416

AC:

11448

AN:

27538

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

6052

12104

18156

24208

30260

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.422

AC:

64231

AN:

152062

Hom.:

13837

Cov.:

AF XY:

0.417

AC XY:

31017

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.398

AC:

16511

AN:

41488

American (AMR)

AF:

0.332

AC:

5066

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.390

AC:

1355

AN:

3470

East Asian (EAS)

AF:

0.303

AC:

1565

AN:

5168

South Asian (SAS)

AF:

0.425

AC:

2044

AN:

4812

European-Finnish (FIN)

AF:

0.429

AC:

4534

AN:

10572

Middle Eastern (MID)

AF:

0.303

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.466

AC:

31684

AN:

67964

Other (OTH)

AF:

0.425

AC:

898

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1887

3775

5662

7550

9437

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.437

Hom.:

29042

Bravo

AF:

0.412

Asia WGS

AF:

0.373

AC:

1298

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.43

(source)

DANN

Benign

0.41

PhyloP100

-0.96

PromoterAI

0.0044

Neutral

(source)

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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rs10510149

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over