dbSNP rs2027515: UROS:c.394+150A>G (chr10-125807263-T-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+150A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.758 in 714,674 control chromosomes in the GnomAD database, including 207,539 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.72 ( 40594 hom., cov: 32)

Exomes 𝑓: 0.77 ( 166945 hom. )

Consequence

UROS
NM_000375.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.94

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 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=-0.91).

BP6

Variant 10-125807263-T-C is Benign according to our data. Variant chr10-125807263-T-C is described in ClinVar as [Benign]. Clinvar id is 1276252.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.785 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UROS	NM_000375.3 link	c.394+150A>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+150A>G		intron_variant	Intron 6 of 9	1	NM_000375.3	ENSP00000357787.4		P10746

Frequencies

GnomAD3 genomes

AF:

0.724

AC:

110081

AN:

151972

Hom.:

40574

Cov.:

show subpopulations

Gnomad AFR

AF:

0.617

Gnomad AMI

AF:

0.809

Gnomad AMR

AF:

0.623

Gnomad ASJ

AF:

0.745

Gnomad EAS

AF:

0.704

Gnomad SAS

AF:

0.775

Gnomad FIN

AF:

0.840

Gnomad MID

AF:

0.614

Gnomad NFE

AF:

0.791

Gnomad OTH

AF:

0.716

GnomAD4 exome

AF:

0.767

AC:

431568

AN:

562584

Hom.:

166945

Cov.:

AF XY:

0.769

AC XY:

231603

AN XY:

301138

show subpopulations

African (AFR)

AF:

0.620

AC:

9376

AN:

15128

American (AMR)

AF:

0.585

AC:

17832

AN:

30474

Ashkenazi Jewish (ASJ)

AF:

0.751

AC:

13551

AN:

18048

East Asian (EAS)

AF:

0.681

AC:

21650

AN:

31796

South Asian (SAS)

AF:

0.775

AC:

44901

AN:

57948

European-Finnish (FIN)

AF:

0.846

AC:

28991

AN:

34276

Middle Eastern (MID)

AF:

0.690

AC:

1690

AN:

2450

European-Non Finnish (NFE)

AF:

0.792

AC:

270916

AN:

342192

Other (OTH)

AF:

0.749

AC:

22661

AN:

30272

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

5229

10458

15687

20916

26145

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.724

AC:

110150

AN:

152090

Hom.:

40594

Cov.:

AF XY:

0.726

AC XY:

53952

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.617

AC:

25589

AN:

41460

American (AMR)

AF:

0.623

AC:

9513

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.745

AC:

2582

AN:

3468

East Asian (EAS)

AF:

0.704

AC:

3643

AN:

5178

South Asian (SAS)

AF:

0.774

AC:

3724

AN:

4810

European-Finnish (FIN)

AF:

0.840

AC:

8886

AN:

10584

Middle Eastern (MID)

AF:

0.619

AC:

182

AN:

294

European-Non Finnish (NFE)

AF:

0.791

AC:

53778

AN:

68008

Other (OTH)

AF:

0.718

AC:

1515

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1503

3006

4508

6011

7514

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.736

Hom.:

18096

Bravo

AF:

0.702

Asia WGS

AF:

0.731

AC:

2546

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

-0.91

CADD

Benign

0.051

(source)

DANN

Benign

0.46

PhyloP100

-3.9

PromoterAI

0.038

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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rs2027515

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over