chr1-97078208-C-T

Variant names:

• chr1-97078208-C-T
• rs291592
• NM_000110.4:c.*768G>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.*768G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 152,410 control chromosomes in the GnomAD database, including 17,089 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.45 (17004 hom., cov: 32)
  • Exomes 𝑓: 0.52 (85 hom.)
• Consequence: DPYD NM_000110.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2 O:1
• Conservation: PhyloP100: 0.145
• Publications: 17 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

ENSG00000296260 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 1-97078208-C-T is Benign according to our data. Variant chr1-97078208-C-T is described in ClinVar as Benign. ClinVar VariationId is 100065.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.948 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.*768G>A		3_prime_UTR	Exon 23 of 23	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.*768G>A		3_prime_UTR	Exon 23 of 23	ENSP00000359211.3	Q12882-1
	DPYD	ENST00000876340.1		c.*768G>A		3_prime_UTR	Exon 24 of 24	ENSP00000546399.1
	DPYD	ENST00000969915.1		c.*768G>A		3_prime_UTR	Exon 24 of 24	ENSP00000639974.1

Frequencies

GnomAD3 genomes AF: 0.452 AC: 68577 AN: 151720 Hom.: 16990 Cov.: 32

Gnomad AFR AF: 0.317

Gnomad AMI AF: 0.416

Gnomad AMR AF: 0.575

Gnomad ASJ AF: 0.452

Gnomad EAS AF: 0.971

Gnomad SAS AF: 0.615

Gnomad FIN AF: 0.479

Gnomad MID AF: 0.328

Gnomad NFE AF: 0.453

Gnomad OTH AF: 0.430

GnomAD4 exome AF: 0.524 AC: 300 AN: 572 Hom.: 85 Cov.: 0 AF XY: 0.533 AC XY: 163 AN XY: 306

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AF: 0.675 AC: 77 AN: 114

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 1.00 AC: 2 AN: 2

South Asian (SAS) AF: 0.553 AC: 21 AN: 38

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.487 AC: 195 AN: 400

Other (OTH) AF: 0.250 AC: 4 AN: 16

GnomAD4 genome AF: 0.452 AC: 68629 AN: 151838 Hom.: 17004 Cov.: 32 AF XY: 0.461 AC XY: 34193 AN XY: 74220

African (AFR) AF: 0.317 AC: 13127 AN: 41410

American (AMR) AF: 0.575 AC: 8768 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.452 AC: 1561 AN: 3452

East Asian (EAS) AF: 0.971 AC: 5005 AN: 5156

South Asian (SAS) AF: 0.615 AC: 2961 AN: 4816

European-Finnish (FIN) AF: 0.479 AC: 5054 AN: 10548

Middle Eastern (MID) AF: 0.322 AC: 94 AN: 292

European-Non Finnish (NFE) AF: 0.453 AC: 30766 AN: 67908

Other (OTH) AF: 0.435 AC: 914 AN: 2102

Alfa AF: 0.456 Hom.: 50442

Bravo AF: 0.456

Asia WGS AF: 0.775 AC: 2691 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Dihydropyrimidine dehydrogenase deficiency (1)
-	-	1	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.2
DANN	Benign	0.50
PhyloP100		0.14
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: rs291592; hg19: chr1-97543764;