rs56279424

chr1-97382584-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate 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, single submitter B:1
• Conservation: PhyloP100: 0.0870

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]

LOC105378867 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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/exons	MANE	UniProt
DPYD	NM_000110.4	c.1906-123C>A		intron_variant		ENST00000370192.8
LOC105378867	XR_007066237.1	n.4218-1050G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DPYD	ENST00000370192.8	c.1906-123C>A		intron_variant		1	NM_000110.4	P1

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

Gnomad4 AFR exome AF: 0.168

Gnomad4 AMR exome AF: 0.145

Gnomad4 ASJ exome AF: 0.241

Gnomad4 EAS exome AF: 0.200

Gnomad4 SAS exome AF: 0.366

Gnomad4 FIN exome AF: 0.167

Gnomad4 NFE exome AF: 0.198

Gnomad4 OTH exome AF: 0.214

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

Gnomad4 AFR AF: 0.166

Gnomad4 AMR AF: 0.168

Gnomad4 ASJ AF: 0.254

Gnomad4 EAS AF: 0.236

Gnomad4 SAS AF: 0.374

Gnomad4 FIN AF: 0.160

Gnomad4 NFE AF: 0.200

Gnomad4 OTH AF: 0.199

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

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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

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

Publications

LitVar

Other links and lift over

dbSNP: rs56279424; hg19: chr1-97848140;