1-97079215-T-C

Variant names:

• chr1-97079215-T-C
• rs290855
• NM_000110.4:c.2908-69A>G

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.2908-69A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.829 in 1,566,256 control chromosomes in the GnomAD database, including 539,716 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.80 (49303 hom., cov: 31)
  • Exomes 𝑓: 0.83 (490413 hom.)
• Consequence: DPYD NM_000110.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.557
• Publications: 7 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=-0.9).
• BP6: Variant 1-97079215-T-C is Benign according to our data. Variant chr1-97079215-T-C is described in ClinVar as Benign. ClinVar VariationId is 1222833.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.966 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPYD	NM_000110.4	c.2908-69A>G		intron_variant	Intron 22 of 22	ENST00000370192.8	NP_000101.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPYD	ENST00000370192.8	c.2908-69A>G		intron_variant	Intron 22 of 22	1	NM_000110.4	ENSP00000359211.3
ENSG00000296260	ENST00000737657.1	n.550-2532T>C		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.802 AC: 121924 AN: 151960 Hom.: 49271 Cov.: 31

Gnomad AFR AF: 0.710

Gnomad AMI AF: 0.884

Gnomad AMR AF: 0.868

Gnomad ASJ AF: 0.847

Gnomad EAS AF: 0.988

Gnomad SAS AF: 0.892

Gnomad FIN AF: 0.839

Gnomad MID AF: 0.820

Gnomad NFE AF: 0.813

Gnomad OTH AF: 0.816

GnomAD4 exome AF: 0.831 AC: 1175814 AN: 1414178 Hom.: 490413 AF XY: 0.833 AC XY: 588326 AN XY: 706420

African (AFR) AF: 0.705 AC: 22850 AN: 32390

American (AMR) AF: 0.889 AC: 39603 AN: 44534

Ashkenazi Jewish (ASJ) AF: 0.840 AC: 21682 AN: 25798

East Asian (EAS) AF: 0.994 AC: 39158 AN: 39414

South Asian (SAS) AF: 0.902 AC: 76742 AN: 85094

European-Finnish (FIN) AF: 0.838 AC: 44652 AN: 53314

Middle Eastern (MID) AF: 0.831 AC: 3435 AN: 4132

European-Non Finnish (NFE) AF: 0.821 AC: 879069 AN: 1070872

Other (OTH) AF: 0.829 AC: 48623 AN: 58630

GnomAD4 genome AF: 0.802 AC: 122014 AN: 152078 Hom.: 49303 Cov.: 31 AF XY: 0.808 AC XY: 60087 AN XY: 74362

African (AFR) AF: 0.711 AC: 29458 AN: 41454

American (AMR) AF: 0.868 AC: 13249 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.847 AC: 2938 AN: 3470

East Asian (EAS) AF: 0.988 AC: 5109 AN: 5170

South Asian (SAS) AF: 0.892 AC: 4303 AN: 4822

European-Finnish (FIN) AF: 0.839 AC: 8893 AN: 10598

Middle Eastern (MID) AF: 0.813 AC: 239 AN: 294

European-Non Finnish (NFE) AF: 0.813 AC: 55294 AN: 67982

Other (OTH) AF: 0.817 AC: 1725 AN: 2112

Alfa AF: 0.814 Hom.: 83738

Bravo AF: 0.802

Asia WGS AF: 0.913 AC: 3175 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.1
DANN	Benign	0.24
PhyloP100		0.56
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: rs290855; hg19: chr1-97544771;