1-97137438-A-G

Variant names:

• chr1-97137438-A-G
• rs1760217
• NM_000110.4:c.2623-38806T>C

Variant summary

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

The NM_000110.4(DPYD):​c.2623-38806T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 152,202 control chromosomes in the GnomAD database, including 2,916 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 (2916 hom., cov: 33)
• Consequence: DPYD NM_000110.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.618
• Publications: 14 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=-0.58).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPYD	NM_000110.4	c.2623-38806T>C		intron_variant	Intron 20 of 22	ENST00000370192.8	NP_000101.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPYD	ENST00000370192.8	c.2623-38806T>C		intron_variant	Intron 20 of 22	1	NM_000110.4	ENSP00000359211.3
DPYD-AS1	ENST00000422980.1	n.64+41452A>G		intron_variant	Intron 1 of 4	3

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29457 AN: 152084 Hom.: 2909 Cov.: 33

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.0857

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.314

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.198

Gnomad OTH AF: 0.200

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

GnomAD4 genome AF: 0.194 AC: 29479 AN: 152202 Hom.: 2916 Cov.: 33 AF XY: 0.192 AC XY: 14285 AN XY: 74416

African (AFR) AF: 0.188 AC: 7809 AN: 41534

American (AMR) AF: 0.206 AC: 3147 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.210 AC: 728 AN: 3466

East Asian (EAS) AF: 0.314 AC: 1620 AN: 5164

South Asian (SAS) AF: 0.156 AC: 753 AN: 4826

European-Finnish (FIN) AF: 0.129 AC: 1372 AN: 10620

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.198 AC: 13480 AN: 68004

Other (OTH) AF: 0.201 AC: 425 AN: 2110

Alfa AF: 0.202 Hom.: 10076

Bravo AF: 0.201

Asia WGS AF: 0.232 AC: 806 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	4.3
DANN	Benign	0.78
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: rs1760217; hg19: chr1-97602994;