Variant rs56276561 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_000110.4(DPYD):c.483+18G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0188 in 1,610,268 control chromosomes in the GnomAD database, including 353 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.013 ( 21 hom., cov: 32)

Exomes 𝑓: 0.019 ( 332 hom. )

Consequence

DPYD
NM_000110.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1O:1

Conservation

PhyloP100: -0.246

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

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

BP6

Variant 1-97721492-C-T is Benign according to our data. Variant chr1-97721492-C-T is described in ClinVar as [Benign]. Clinvar id is 100117.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0133 (2011/151696) while in subpopulation NFE AF= 0.0212 (1435/67724). AF 95% confidence interval is 0.0203. There are 21 homozygotes in gnomad4. There are 954 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 21 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DPYD	NM_000110.4 linkuse as main transcript	c.483+18G>A		intron_variant		ENST00000370192.8

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
DPYD	ENST00000370192.8 linkuse as main transcript	c.483+18G>A	intron_variant	1	NM_000110.4	P1	Q12882-1
DPYD	ENST00000306031.5 linkuse as main transcript	c.483+18G>A	intron_variant	1			Q12882-2
DPYD	ENST00000474241.1 linkuse as main transcript	n.145+18G>A	intron_variant, non_coding_transcript_variant	3

Frequencies

GnomAD3 genomes

AF:

0.0133

AC:

2011

AN:

151578

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00310

Gnomad AMI

AF:

0.0285

Gnomad AMR

AF:

0.00759

Gnomad ASJ

AF:

0.00809

Gnomad EAS

AF:

0.000580

Gnomad SAS

AF:

0.0199

Gnomad FIN

AF:

0.0143

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0212

Gnomad OTH

AF:

0.0101

GnomAD3 exomes

AF:

0.0145

AC:

3628

AN:

250088

Hom.:

AF XY:

0.0157

AC XY:

2121

AN XY:

135160

show subpopulations

Gnomad AFR exome

AF:

0.00296

Gnomad AMR exome

AF:

0.00459

Gnomad ASJ exome

AF:

0.00779

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0192

Gnomad FIN exome

AF:

0.0124

Gnomad NFE exome

AF:

0.0213

Gnomad OTH exome

AF:

0.0143

GnomAD4 exome

AF:

0.0194

AC:

28299

AN:

1458572

Hom.:

332

Cov.:

AF XY:

0.0195

AC XY:

14171

AN XY:

725612

show subpopulations

Gnomad4 AFR exome

AF:

0.00288

Gnomad4 AMR exome

AF:

0.00494

Gnomad4 ASJ exome

AF:

0.00697

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0201

Gnomad4 FIN exome

AF:

0.0132

Gnomad4 NFE exome

AF:

0.0219

Gnomad4 OTH exome

AF:

0.0163

GnomAD4 genome

AF:

0.0133

AC:

2011

AN:

151696

Hom.:

Cov.:

AF XY:

0.0129

AC XY:

954

AN XY:

74134

show subpopulations

Gnomad4 AFR

AF:

0.00306

Gnomad4 AMR

AF:

0.00758

Gnomad4 ASJ

AF:

0.00809

Gnomad4 EAS

AF:

0.000582

Gnomad4 SAS

AF:

0.0199

Gnomad4 FIN

AF:

0.0143

Gnomad4 NFE

AF:

0.0212

Gnomad4 OTH

AF:

0.0105

Alfa

AF:

0.0153

Hom.:

Bravo

AF:

0.0121

Asia WGS

AF:

0.0100

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1Other:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Other:1

not provided, no classification provided

literature only

Diasio Lab, Mayo Clinic

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.059

DANN

Benign

0.37

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