1-97144470-G-T

Variant names:

• chr1-97144470-G-T
• rs828054
• NM_000110.4:c.2623-45838C>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.2623-45838C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.628 in 152,104 control chromosomes in the GnomAD database, including 31,946 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 0.63 (31946 hom., cov: 33)
• Consequence: DPYD NM_000110.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.534
• Publications: 4 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.968 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.2623-45838C>A		intron	N/A	NP_000101.2
	DPYD-AS1	NR_046590.1		n.64+48484G>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.2623-45838C>A		intron	N/A	ENSP00000359211.3
	DPYD	ENST00000876340.1		c.2791-45838C>A		intron	N/A	ENSP00000546399.1
	DPYD	ENST00000969915.1		c.2727+26691C>A		intron	N/A	ENSP00000639974.1

Frequencies

GnomAD3 genomes AF: 0.628 AC: 95425 AN: 151986 Hom.: 31902 Cov.: 33

Gnomad AFR AF: 0.823

Gnomad AMI AF: 0.460

Gnomad AMR AF: 0.620

Gnomad ASJ AF: 0.492

Gnomad EAS AF: 0.991

Gnomad SAS AF: 0.798

Gnomad FIN AF: 0.500

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.501

Gnomad OTH AF: 0.604

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

GnomAD4 genome AF: 0.628 AC: 95529 AN: 152104 Hom.: 31946 Cov.: 33 AF XY: 0.633 AC XY: 47082 AN XY: 74352

African (AFR) AF: 0.823 AC: 34162 AN: 41526

American (AMR) AF: 0.621 AC: 9474 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.492 AC: 1704 AN: 3466

East Asian (EAS) AF: 0.991 AC: 5120 AN: 5166

South Asian (SAS) AF: 0.799 AC: 3852 AN: 4822

European-Finnish (FIN) AF: 0.500 AC: 5294 AN: 10578

Middle Eastern (MID) AF: 0.571 AC: 168 AN: 294

European-Non Finnish (NFE) AF: 0.501 AC: 34054 AN: 67962

Other (OTH) AF: 0.606 AC: 1282 AN: 2114

Alfa AF: 0.536 Hom.: 36497

Bravo AF: 0.645

Asia WGS AF: 0.875 AC: 3037 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.6
DANN	Benign	0.56
PhyloP100		0.53
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: rs828054; hg19: chr1-97610026;