1-97382584-G-T

Variant names:

• chr1-97382584-G-T
• rs56279424
• NM_000110.4:c.1906-123C>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.1906-123C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 534,586 control chromosomes in the GnomAD database, including 11,511 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.19 (2984 hom., cov: 33)
  • Exomes 𝑓: 0.20 (8527 hom.)
• Consequence: DPYD NM_000110.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0870
• Publications: 3 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

LOC105378867 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 1-97382584-G-T is Benign according to our data. Variant chr1-97382584-G-T is described in ClinVar as [Benign]. Clinvar id is 1232655.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.359 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPYD	NM_000110.4	c.1906-123C>A		intron_variant	Intron 14 of 22	ENST00000370192.8	NP_000101.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPYD	ENST00000370192.8	c.1906-123C>A		intron_variant	Intron 14 of 22	1	NM_000110.4	ENSP00000359211.3

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29195 AN: 151934 Hom.: 2986 Cov.: 33

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.236

Gnomad SAS AF: 0.374

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.197

GnomAD4 exome AF: 0.203 AC: 77592 AN: 382534 Hom.: 8527 AF XY: 0.206 AC XY: 41459 AN XY: 200924

African (AFR) AF: 0.168 AC: 1505 AN: 8944

American (AMR) AF: 0.145 AC: 1523 AN: 10490

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 2589 AN: 10746

East Asian (EAS) AF: 0.200 AC: 4667 AN: 23348

South Asian (SAS) AF: 0.366 AC: 6228 AN: 17008

European-Finnish (FIN) AF: 0.167 AC: 5443 AN: 32674

Middle Eastern (MID) AF: 0.243 AC: 363 AN: 1492

European-Non Finnish (NFE) AF: 0.198 AC: 50947 AN: 257576

Other (OTH) AF: 0.214 AC: 4327 AN: 20256

GnomAD4 genome AF: 0.192 AC: 29212 AN: 152052 Hom.: 2984 Cov.: 33 AF XY: 0.193 AC XY: 14318 AN XY: 74322

African (AFR) AF: 0.166 AC: 6882 AN: 41508

American (AMR) AF: 0.168 AC: 2557 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.254 AC: 881 AN: 3470

East Asian (EAS) AF: 0.236 AC: 1219 AN: 5168

South Asian (SAS) AF: 0.374 AC: 1803 AN: 4826

European-Finnish (FIN) AF: 0.160 AC: 1686 AN: 10542

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

European-Non Finnish (NFE) AF: 0.200 AC: 13582 AN: 67968

Other (OTH) AF: 0.199 AC: 419 AN: 2108

Alfa AF: 0.190 Hom.: 360

Bravo AF: 0.187

Asia WGS AF: 0.325 AC: 1127 AN: 3470

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jul 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.2
DANN	Benign	0.19
PhyloP100		0.087
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: rs56279424; hg19: chr1-97848140;