Genetic Variant UROD:c.21-10T>C (chr1-45012897-T-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000374.5(UROD):c.21-10T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.0 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000012 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

UROD
NM_000374.5 intron

Scores

Splicing: ADA: 0.0002262

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.445

Publications

0 publications found

Variant links:

Genes affected

UROD (HGNC:12591): (uroporphyrinogen decarboxylase) This gene encodes an enzyme in the heme biosynthetic pathway. This enzyme is responsible for catalyzing the conversion of uroporphyrinogen to coproporphyrinogen through the removal of four carboxymethyl side chains. Mutations and deficiency in this enzyme are known to cause familial porphyria cutanea tarda and hepatoerythropoetic porphyria.[provided by RefSeq, Aug 2010]

UROD Gene-Disease associations (from GenCC):

UROD-related inherited porphyria
Inheritance: SD Classification: DEFINITIVE Submitted by: ClinGen, Ambry Genetics
familial porphyria cutanea tarda
Inheritance: AD, AR Classification: STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet, Labcorp Genetics (formerly Invitae)
hepatoerythropoietic porphyria
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

UROD links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000374.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
UROD	NM_000374.5	MANE Select	c.21-10T>C	intron	N/A	NP_000365.3
UROD	NR_036510.2		n.73T>C	non_coding_transcript_exon	Exon 2 of 10
UROD	NR_158184.1		n.73T>C	non_coding_transcript_exon	Exon 2 of 10

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
UROD	ENST00000246337.9	TSL:1 MANE Select	c.21-10T>C	intron	N/A	ENSP00000246337.4	P06132
UROD	ENST00000461035.5	TSL:1	n.115T>C	non_coding_transcript_exon	Exon 2 of 4
UROD	ENST00000651476.1		c.-95T>C	5_prime_UTR	Exon 2 of 10	ENSP00000498668.1	A0A494C0Q8

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

141534

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000119

AC:

AN:

839102

Hom.:

Cov.:

AF XY:

0.00000231

AC XY:

AN XY:

432180

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

19454

American (AMR)

AF:

0.00

AC:

AN:

38608

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16998

East Asian (EAS)

AF:

0.00

AC:

AN:

20178

South Asian (SAS)

AF:

0.00

AC:

AN:

75328

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37082

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3982

European-Non Finnish (NFE)

AF:

0.00000169

AC:

AN:

593334

Other (OTH)

AF:

0.00

AC:

AN:

34138

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

141534

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

68660

African (AFR)

AF:

0.00

AC:

AN:

38788

American (AMR)

AF:

0.00

AC:

AN:

14328

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3322

East Asian (EAS)

AF:

0.00

AC:

AN:

4226

South Asian (SAS)

AF:

0.00

AC:

AN:

4044

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8918

Middle Eastern (MID)

AF:

0.00

AC:

AN:

302

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

64744

Other (OTH)

AF:

0.00

AC:

AN:

1994

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

9.3

(source)

DANN

Benign

0.70

PhyloP100

0.45

PromoterAI

0.12

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00023

dbscSNV1_RF

Benign

0.062

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over