rs12137711

Variant names:

• chr1-97235033-C-T
• rs12137711
• NM_000110.4:c.2300-39G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000110.4(DPYD):​c.2300-39G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 1,611,754 control chromosomes in the GnomAD database, including 11,961 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.095 (897 hom., cov: 32)
  • Exomes 𝑓: 0.12 (11064 hom.)
• Consequence: DPYD NM_000110.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2 O:1
• Conservation: PhyloP100: -0.0120
• Publications: 12 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 1-97235033-C-T is Benign according to our data. Variant chr1-97235033-C-T is described in ClinVar as Benign. ClinVar VariationId is 100076.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.209 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.2300-39G>A		intron	N/A	NP_000101.2
	DPYD-AS1	NR_046590.1		n.65-30381C>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.2300-39G>A		intron	N/A	ENSP00000359211.3
	DPYD-AS1	ENST00000422980.1	TSL:3	n.65-30381C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0947 AC: 14411 AN: 152132 Hom.: 899 Cov.: 32

Gnomad AFR AF: 0.0267

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.0936

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.0433

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.112

GnomAD2 exomes AF: 0.119 AC: 29669 AN: 249794 AF XY: 0.129

Gnomad AFR exome AF: 0.0245

Gnomad AMR exome AF: 0.0751

Gnomad ASJ exome AF: 0.120

Gnomad EAS exome AF: 0.0374

Gnomad FIN exome AF: 0.187

Gnomad NFE exome AF: 0.115

Gnomad OTH exome AF: 0.138

GnomAD4 exome AF: 0.115 AC: 168469 AN: 1459504 Hom.: 11064 Cov.: 32 AF XY: 0.120 AC XY: 86934 AN XY: 726138

African (AFR) AF: 0.0253 AC: 845 AN: 33440

American (AMR) AF: 0.0767 AC: 3427 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 3203 AN: 26124

East Asian (EAS) AF: 0.0428 AC: 1697 AN: 39660

South Asian (SAS) AF: 0.226 AC: 19501 AN: 86116

European-Finnish (FIN) AF: 0.186 AC: 9882 AN: 53246

Middle Eastern (MID) AF: 0.195 AC: 1126 AN: 5766

European-Non Finnish (NFE) AF: 0.110 AC: 121684 AN: 1110110

Other (OTH) AF: 0.118 AC: 7104 AN: 60334

GnomAD4 genome AF: 0.0947 AC: 14413 AN: 152250 Hom.: 897 Cov.: 32 AF XY: 0.101 AC XY: 7541 AN XY: 74458

African (AFR) AF: 0.0268 AC: 1114 AN: 41554

American (AMR) AF: 0.0934 AC: 1429 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 430 AN: 3468

East Asian (EAS) AF: 0.0434 AC: 225 AN: 5186

South Asian (SAS) AF: 0.220 AC: 1060 AN: 4826

European-Finnish (FIN) AF: 0.191 AC: 2023 AN: 10588

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.114 AC: 7750 AN: 68010

Other (OTH) AF: 0.113 AC: 239 AN: 2114

Alfa AF: 0.110 Hom.: 1858

Bravo AF: 0.0807

Asia WGS AF: 0.133 AC: 464 AN: 3476

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.9
DANN	Benign	0.65
PhyloP100		-0.012
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: rs12137711; hg19: chr1-97700589;