NM_000110.4:c.2622+5555G>A

Variant names:

• chr1-97187514-C-T
• rs11587873
• NM_000110.4:c.2622+5555G>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.2622+5555G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 152,042 control chromosomes in the GnomAD database, including 2,666 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 0.17 (2666 hom., cov: 32)
• Consequence: DPYD NM_000110.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.281
• Publications: 6 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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.24 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.2622+5555G>A		intron	N/A	NP_000101.2
	DPYD-AS1	NR_046590.1		n.65-77900C>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.2622+5555G>A		intron	N/A	ENSP00000359211.3
	DPYD-AS1	ENST00000422980.1	TSL:3	n.65-77900C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.171 AC: 25915 AN: 151922 Hom.: 2669 Cov.: 32

Gnomad AFR AF: 0.0710

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.0501

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.242

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.197

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

GnomAD4 genome AF: 0.170 AC: 25915 AN: 152042 Hom.: 2666 Cov.: 32 AF XY: 0.173 AC XY: 12844 AN XY: 74310

African (AFR) AF: 0.0711 AC: 2951 AN: 41530

American (AMR) AF: 0.149 AC: 2267 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.254 AC: 883 AN: 3470

East Asian (EAS) AF: 0.0502 AC: 260 AN: 5176

South Asian (SAS) AF: 0.252 AC: 1213 AN: 4812

European-Finnish (FIN) AF: 0.242 AC: 2545 AN: 10514

Middle Eastern (MID) AF: 0.271 AC: 79 AN: 292

European-Non Finnish (NFE) AF: 0.222 AC: 15098 AN: 67968

Other (OTH) AF: 0.195 AC: 412 AN: 2108

Alfa AF: 0.215 Hom.: 5996

Bravo AF: 0.158

Asia WGS AF: 0.142 AC: 494 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.4
DANN	Benign	0.33
PhyloP100		0.28
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: rs11587873; hg19: chr1-97653070;