rs6683957

Positions:

• chr1-97735163-A-G
• chr1-97735163-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000110.4(DPYD):​c.321+5229T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.855 in 152,054 control chromosomes in the GnomAD database, including 56,091 homozygotes. 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 0.85 (56091 hom., cov: 30)
• Consequence: DPYD NM_000110.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.68

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.962 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DPYD	NM_000110.4	c.321+5229T>C		intron_variant		ENST00000370192.8	NP_000101.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DPYD	ENST00000370192.8	c.321+5229T>C		intron_variant		1	NM_000110.4	ENSP00000359211	P1
DPYD	ENST00000306031.5	c.321+5229T>C		intron_variant		1		ENSP00000307107

Frequencies

GnomAD3 genomes AF: 0.855 AC: 129905 AN: 151936 Hom.: 56073 Cov.: 30

Gnomad AFR AF: 0.720

Gnomad AMI AF: 0.861

Gnomad AMR AF: 0.912

Gnomad ASJ AF: 0.925

Gnomad EAS AF: 0.985

Gnomad SAS AF: 0.914

Gnomad FIN AF: 0.850

Gnomad MID AF: 0.851

Gnomad NFE AF: 0.907

Gnomad OTH AF: 0.875

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.855 AC: 129965 AN: 152054 Hom.: 56091 Cov.: 30 AF XY: 0.853 AC XY: 63431 AN XY: 74322

Gnomad4 AFR AF: 0.719

Gnomad4 AMR AF: 0.913

Gnomad4 ASJ AF: 0.925

Gnomad4 EAS AF: 0.985

Gnomad4 SAS AF: 0.914

Gnomad4 FIN AF: 0.850

Gnomad4 NFE AF: 0.907

Gnomad4 OTH AF: 0.876

Alfa AF: 0.901 Hom.: 83607

Bravo AF: 0.854

Asia WGS AF: 0.923 AC: 3209 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.3
DANN	Benign	0.79

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

Other links and lift over

dbSNP: rs6683957; hg19: chr1-98200719;