Variant rs12137711 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000110.4(DPYD):c.2300-39G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 1,611,754 control chromosomes in the GnomAD database, including 11,961 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.095 ( 897 hom., cov: 32)

Exomes 𝑓: 0.12 ( 11064 hom. )

Consequence

DPYD
NM_000110.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2O:1

Conservation

PhyloP100: -0.0120

Variant links:

Genes affected

DPYD (HGNC:3012): (dihydropyrimidine dehydrogenase) The protein encoded by this gene is a pyrimidine catabolic enzyme and the initial and rate-limiting factor in the pathway of uracil and thymidine catabolism. Mutations in this gene result in dihydropyrimidine dehydrogenase deficiency, an error in pyrimidine metabolism associated with thymine-uraciluria and an increased risk of toxicity in cancer patients receiving 5-fluorouracil chemotherapy. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2009]

DPYD links:

DPYD-AS1 (HGNC:40195): (DPYD antisense RNA 1)

DPYD-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 1-97235033-C-T is Benign according to our data. Variant chr1-97235033-C-T is described in ClinVar as [Benign]. Clinvar id is 100076.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DPYD	NM_000110.4 linkuse as main transcript	c.2300-39G>A		intron_variant		ENST00000370192.8	NP_000101.2
DPYD-AS1	NR_046590.1 linkuse as main transcript	n.65-30381C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DPYD	ENST00000370192.8 linkuse as main transcript	c.2300-39G>A		intron_variant		1	NM_000110.4	ENSP00000359211	P1	Q12882-1
DPYD-AS1	ENST00000422980.1 linkuse as main transcript	n.65-30381C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0947

AC:

14411

AN:

152132

Hom.:

899

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0267

Gnomad AMI

AF:

0.116

Gnomad AMR

AF:

0.0936

Gnomad ASJ

AF:

0.124

Gnomad EAS

AF:

0.0433

Gnomad SAS

AF:

0.220

Gnomad FIN

AF:

0.191

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.114

Gnomad OTH

AF:

0.112

GnomAD3 exomes

AF:

0.119

AC:

29669

AN:

249794

Hom.:

2238

AF XY:

0.129

AC XY:

17388

AN XY:

135098

show subpopulations

Gnomad AFR exome

AF:

0.0245

Gnomad AMR exome

AF:

0.0751

Gnomad ASJ exome

AF:

0.120

Gnomad EAS exome

AF:

0.0374

Gnomad SAS exome

AF:

0.229

Gnomad FIN exome

AF:

0.187

Gnomad NFE exome

AF:

0.115

Gnomad OTH exome

AF:

0.138

GnomAD4 exome

AF:

0.115

AC:

168469

AN:

1459504

Hom.:

11064

Cov.:

AF XY:

0.120

AC XY:

86934

AN XY:

726138

show subpopulations

Gnomad4 AFR exome

AF:

0.0253

Gnomad4 AMR exome

AF:

0.0767

Gnomad4 ASJ exome

AF:

0.123

Gnomad4 EAS exome

AF:

0.0428

Gnomad4 SAS exome

AF:

0.226

Gnomad4 FIN exome

AF:

0.186

Gnomad4 NFE exome

AF:

0.110

Gnomad4 OTH exome

AF:

0.118

GnomAD4 genome

AF:

0.0947

AC:

14413

AN:

152250

Hom.:

897

Cov.:

AF XY:

0.101

AC XY:

7541

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.0268

Gnomad4 AMR

AF:

0.0934

Gnomad4 ASJ

AF:

0.124

Gnomad4 EAS

AF:

0.0434

Gnomad4 SAS

AF:

0.220

Gnomad4 FIN

AF:

0.191

Gnomad4 NFE

AF:

0.114

Gnomad4 OTH

AF:

0.113

Alfa

AF:

0.114

Hom.:

1528

Bravo

AF:

0.0807

Asia WGS

AF:

0.133

AC:

464

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:2Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2Other:1

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -
not provided, no classification provided	literature only	Diasio Lab, Mayo Clinic	-	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

1.9

DANN

Benign

0.65

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over