1-97111366-C-T

Variant names:

• chr1-97111366-C-T
• rs1399291
• NM_000110.4:c.2623-12734G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000110.4(DPYD):​c.2623-12734G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 151,816 control chromosomes in the GnomAD database, including 16,373 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 0.44 (16373 hom., cov: 32)
• Consequence: DPYD NM_000110.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.621
• Publications: 12 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.951 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000110.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPYD	NM_000110.4	MANE Select	c.2623-12734G>A		intron	N/A	NP_000101.2
	DPYD-AS1	NR_046590.1		n.64+15380C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPYD	ENST00000370192.8	TSL:1 MANE Select	c.2623-12734G>A		intron	N/A	ENSP00000359211.3
	DPYD-AS1	ENST00000422980.1	TSL:3	n.64+15380C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.438 AC: 66478 AN: 151698 Hom.: 16360 Cov.: 32

Gnomad AFR AF: 0.269

Gnomad AMI AF: 0.418

Gnomad AMR AF: 0.567

Gnomad ASJ AF: 0.450

Gnomad EAS AF: 0.973

Gnomad SAS AF: 0.617

Gnomad FIN AF: 0.479

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.453

Gnomad OTH AF: 0.422

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

GnomAD4 genome AF: 0.438 AC: 66521 AN: 151816 Hom.: 16373 Cov.: 32 AF XY: 0.447 AC XY: 33139 AN XY: 74144

African (AFR) AF: 0.269 AC: 11155 AN: 41422

American (AMR) AF: 0.568 AC: 8648 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.450 AC: 1559 AN: 3468

East Asian (EAS) AF: 0.973 AC: 5025 AN: 5164

South Asian (SAS) AF: 0.617 AC: 2963 AN: 4804

European-Finnish (FIN) AF: 0.479 AC: 5048 AN: 10536

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.453 AC: 30744 AN: 67878

Other (OTH) AF: 0.426 AC: 902 AN: 2116

Alfa AF: 0.444 Hom.: 23223

Bravo AF: 0.440

Asia WGS AF: 0.772 AC: 2682 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.54
DANN	Benign	0.36
PhyloP100		-0.62
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1399291; hg19: chr1-97576922;