rs12022243

Positions:

• chr1-97397224-C-T

Variant summary

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

The ENST00000370192.8(DPYD):​c.1906-14763G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 151,802 control chromosomes in the GnomAD database, including 2,930 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 0.19 (2930 hom., cov: 32)
• Consequence: DPYD ENST00000370192.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.450

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-IT1 (HGNC:41326): (DPYD intronic transcript 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.35 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DPYD	NM_000110.4	c.1906-14763G>A		intron_variant		ENST00000370192.8	NP_000101.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DPYD	ENST00000370192.8	c.1906-14763G>A		intron_variant		1	NM_000110.4	ENSP00000359211	P1
DPYD-IT1	ENST00000424982.1	n.136-2805G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29075 AN: 151686 Hom.: 2932 Cov.: 32

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.234

Gnomad SAS AF: 0.365

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.196

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

GnomAD4 genome AF: 0.192 AC: 29092 AN: 151802 Hom.: 2930 Cov.: 32 AF XY: 0.192 AC XY: 14256 AN XY: 74156

Gnomad4 AFR AF: 0.165

Gnomad4 AMR AF: 0.167

Gnomad4 ASJ AF: 0.253

Gnomad4 EAS AF: 0.234

Gnomad4 SAS AF: 0.364

Gnomad4 FIN AF: 0.161

Gnomad4 NFE AF: 0.200

Gnomad4 OTH AF: 0.197

Alfa AF: 0.190 Hom.: 363

Bravo AF: 0.187

Asia WGS AF: 0.323 AC: 1121 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.2
DANN	Benign	0.29

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: rs12022243; hg19: chr1-97862780;