rs12022243

Variant names:

• chr1-97397224-C-T
• rs12022243
• NM_000110.4:c.1906-14763G>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.1906-14763G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 151,802 control chromosomes in the GnomAD database, including 2,930 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 (2930 hom., cov: 32)
• Consequence: DPYD NM_000110.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.450
• 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-IT1 (HGNC:41326): (DPYD intronic transcript 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.35 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.1906-14763G>A		intron	N/A	NP_000101.2	Q12882-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPYD	ENST00000370192.8	TSL:1 MANE Select	c.1906-14763G>A		intron	N/A	ENSP00000359211.3	Q12882-1
	DPYD	ENST00000876340.1		c.2074-14763G>A		intron	N/A	ENSP00000546399.1
	DPYD	ENST00000969915.1		c.1906-14763G>A		intron	N/A	ENSP00000639974.1

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29075 AN: 151686 Hom.: 2932 Cov.: 32

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.234

Gnomad SAS AF: 0.365

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.196

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

GnomAD4 genome AF: 0.192 AC: 29092 AN: 151802 Hom.: 2930 Cov.: 32 AF XY: 0.192 AC XY: 14256 AN XY: 74156

African (AFR) AF: 0.165 AC: 6852 AN: 41406

American (AMR) AF: 0.167 AC: 2547 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.253 AC: 876 AN: 3464

East Asian (EAS) AF: 0.234 AC: 1201 AN: 5126

South Asian (SAS) AF: 0.364 AC: 1749 AN: 4806

European-Finnish (FIN) AF: 0.161 AC: 1691 AN: 10518

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.200 AC: 13578 AN: 67920

Other (OTH) AF: 0.197 AC: 416 AN: 2108

Alfa AF: 0.190 Hom.: 375

Bravo AF: 0.187

Asia WGS AF: 0.323 AC: 1121 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.2
DANN	Benign	0.29
PhyloP100		-0.45
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: rs12022243; hg19: chr1-97862780;