chr1-97767974-G-C

Variant names:

• chr1-97767974-G-C
• rs4537601
• NM_000110.4:c.234-27495C>G

Variant summary

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

The NM_000110.4(DPYD):​c.234-27495C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.748 in 151,894 control chromosomes in the GnomAD database, including 42,959 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 0.75 (42959 hom., cov: 30)
• Consequence: DPYD NM_000110.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0720
• Publications: 5 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 Gene-Disease associations (from GenCC):

• dihydropyrimidine dehydrogenase deficiency

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.96 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPYD	NM_000110.4	MANE Select	c.234-27495C>G		intron	N/A	NP_000101.2	Q12882-1
	DPYD	NM_001160301.1		c.234-27495C>G		intron	N/A	NP_001153773.1	Q12882-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPYD	ENST00000370192.8	TSL:1 MANE Select	c.234-27495C>G		intron	N/A	ENSP00000359211.3	Q12882-1
	DPYD	ENST00000306031.5	TSL:1	c.234-27495C>G		intron	N/A	ENSP00000307107.5	Q12882-2
	DPYD	ENST00000876340.1		c.234-27495C>G		intron	N/A	ENSP00000546399.1

Frequencies

GnomAD3 genomes AF: 0.748 AC: 113565 AN: 151776 Hom.: 42941 Cov.: 30

Gnomad AFR AF: 0.637

Gnomad AMI AF: 0.697

Gnomad AMR AF: 0.825

Gnomad ASJ AF: 0.875

Gnomad EAS AF: 0.982

Gnomad SAS AF: 0.814

Gnomad FIN AF: 0.723

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.774

Gnomad OTH AF: 0.763

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

GnomAD4 genome AF: 0.748 AC: 113622 AN: 151894 Hom.: 42959 Cov.: 30 AF XY: 0.751 AC XY: 55720 AN XY: 74224

African (AFR) AF: 0.636 AC: 26321 AN: 41378

American (AMR) AF: 0.825 AC: 12596 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.875 AC: 3027 AN: 3460

East Asian (EAS) AF: 0.982 AC: 5074 AN: 5166

South Asian (SAS) AF: 0.814 AC: 3922 AN: 4818

European-Finnish (FIN) AF: 0.723 AC: 7608 AN: 10520

Middle Eastern (MID) AF: 0.772 AC: 227 AN: 294

European-Non Finnish (NFE) AF: 0.774 AC: 52594 AN: 67974

Other (OTH) AF: 0.766 AC: 1620 AN: 2116

Alfa AF: 0.754 Hom.: 5107

Bravo AF: 0.751

Asia WGS AF: 0.881 AC: 3051 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.53
PhyloP100		-0.072
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: rs4537601; hg19: chr1-98233530;