1-97192839-C-T

Position:

• chr1-97192839-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000370192.8(DPYD):​c.2622+230G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.649 in 152,012 control chromosomes in the GnomAD database, including 32,407 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.65 (32407 hom., cov: 31)
• Consequence: DPYD ENST00000370192.8 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.800

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

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 1-97192839-C-T is Benign according to our data. Variant chr1-97192839-C-T is described in ClinVar as [Benign]. Clinvar id is 1267185.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.969 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DPYD	NM_000110.4	c.2622+230G>A		intron_variant		ENST00000370192.8	NP_000101.2
DPYD-AS1	NR_046590.1	n.65-72575C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DPYD	ENST00000370192.8	c.2622+230G>A		intron_variant		1	NM_000110.4	ENSP00000359211	P1
DPYD-AS1	ENST00000422980.1	n.65-72575C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.649 AC: 98521 AN: 151894 Hom.: 32375 Cov.: 31

Gnomad AFR AF: 0.656

Gnomad AMI AF: 0.512

Gnomad AMR AF: 0.654

Gnomad ASJ AF: 0.561

Gnomad EAS AF: 0.991

Gnomad SAS AF: 0.815

Gnomad FIN AF: 0.624

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.615

Gnomad OTH AF: 0.644

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

GnomAD4 genome AF: 0.649 AC: 98606 AN: 152012 Hom.: 32407 Cov.: 31 AF XY: 0.654 AC XY: 48594 AN XY: 74302

Gnomad4 AFR AF: 0.656

Gnomad4 AMR AF: 0.655

Gnomad4 ASJ AF: 0.561

Gnomad4 EAS AF: 0.991

Gnomad4 SAS AF: 0.816

Gnomad4 FIN AF: 0.624

Gnomad4 NFE AF: 0.615

Gnomad4 OTH AF: 0.645

Alfa AF: 0.640 Hom.: 11568

Bravo AF: 0.652

Asia WGS AF: 0.869 AC: 3019 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	9.1
DANN	Benign	0.57

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: rs4950023; hg19: chr1-97658395;