1-97192839-C-T

Variant names:

• chr1-97192839-C-T
• rs4950023
• NM_000110.4:c.2622+230G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000110.4(DPYD):​c.2622+230G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.649 in 152,012 control chromosomes in the GnomAD database, including 32,407 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.65 (32407 hom., cov: 31)
• Consequence: DPYD NM_000110.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.800
• Publications: 5 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 1-97192839-C-T is Benign according to our data. Variant chr1-97192839-C-T is described in ClinVar as Benign. ClinVar VariationId is 1267185.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.969 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.2622+230G>A		intron	N/A	NP_000101.2	Q12882-1
	DPYD-AS1	NR_046590.1		n.65-72575C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPYD	ENST00000370192.8	TSL:1 MANE Select	c.2622+230G>A		intron	N/A	ENSP00000359211.3	Q12882-1
	DPYD	ENST00000876340.1		c.2790+230G>A		intron	N/A	ENSP00000546399.1
	DPYD	ENST00000969915.1		c.2622+230G>A		intron	N/A	ENSP00000639974.1

Frequencies

GnomAD3 genomes AF: 0.649 AC: 98521 AN: 151894 Hom.: 32375 Cov.: 31

Gnomad AFR AF: 0.656

Gnomad AMI AF: 0.512

Gnomad AMR AF: 0.654

Gnomad ASJ AF: 0.561

Gnomad EAS AF: 0.991

Gnomad SAS AF: 0.815

Gnomad FIN AF: 0.624

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.615

Gnomad OTH AF: 0.644

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.649 AC: 98606 AN: 152012 Hom.: 32407 Cov.: 31 AF XY: 0.654 AC XY: 48594 AN XY: 74302

African (AFR) AF: 0.656 AC: 27218 AN: 41462

American (AMR) AF: 0.655 AC: 9997 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.561 AC: 1947 AN: 3468

East Asian (EAS) AF: 0.991 AC: 5109 AN: 5154

South Asian (SAS) AF: 0.816 AC: 3932 AN: 4820

European-Finnish (FIN) AF: 0.624 AC: 6586 AN: 10552

Middle Eastern (MID) AF: 0.650 AC: 191 AN: 294

European-Non Finnish (NFE) AF: 0.615 AC: 41800 AN: 67972

Other (OTH) AF: 0.645 AC: 1359 AN: 2108

Alfa AF: 0.636 Hom.: 13950

Bravo AF: 0.652

Asia WGS AF: 0.869 AC: 3019 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	9.1
DANN	Benign	0.57
PhyloP100		0.80
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: rs4950023; hg19: chr1-97658395;