rs2230761

Variant names:

• chr7-48107042-A-G
• rs2230761
• NM_003364.4:c.606A>G

Your query was ambiguous. Multiple possible variants found:

• chr7-48107042-A-G
• chr7-48107042-A-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_003364.4(UPP1):​c.606A>G​(p.Thr202Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00574 in 1,612,346 control chromosomes in the GnomAD database, including 343 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.027 (169 hom., cov: 33)
  • Exomes 𝑓: 0.0036 (174 hom.)
• Consequence: UPP1 NM_003364.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -4.04
• Publications: 2 publications found

Genes affected

UPP1 (HGNC:12576): (uridine phosphorylase 1) This gene encodes a uridine phosphorylase, an enzyme that catalyzes the reversible phosphorylation of uridine (or 2'- deoxyuridine) to uracil and ribose-1-phosphate (or deoxyribose-1-phosphate). The encoded enzyme functions in the degradation and salvage of pyrimidine ribonucleosides. [provided by RefSeq, Oct 2016]

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BP6: Variant 7-48107042-A-G is Benign according to our data. Variant chr7-48107042-A-G is described in ClinVar as Benign. ClinVar VariationId is 769712.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.04 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0878 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003364.4. 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
	UPP1	NM_003364.4	MANE Select	c.606A>G	p.Thr202Thr	synonymous	Exon 7 of 9	NP_003355.1	Q16831-1
	UPP1	NM_001287426.2		c.606A>G	p.Thr202Thr	synonymous	Exon 8 of 10	NP_001274355.1	Q16831-1
	UPP1	NM_001362774.2		c.606A>G	p.Thr202Thr	synonymous	Exon 8 of 10	NP_001349703.1	Q16831-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UPP1	ENST00000395564.9	TSL:1 MANE Select	c.606A>G	p.Thr202Thr	synonymous	Exon 7 of 9	ENSP00000378931.4	Q16831-1
	UPP1	ENST00000331803.8	TSL:1	c.606A>G	p.Thr202Thr	synonymous	Exon 8 of 10	ENSP00000330032.4	Q16831-1
	UPP1	ENST00000417464.6	TSL:1	n.*103A>G		non_coding_transcript_exon	Exon 4 of 6	ENSP00000413611.2	Q16831-2

Frequencies

GnomAD3 genomes AF: 0.0266 AC: 4043 AN: 152172 Hom.: 169 Cov.: 33

Gnomad AFR AF: 0.0903

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00850

Gnomad ASJ AF: 0.00634

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00143

Gnomad OTH AF: 0.0196

GnomAD2 exomes AF: 0.00772 AC: 1939 AN: 251296 AF XY: 0.00619

Gnomad AFR exome AF: 0.0906

Gnomad AMR exome AF: 0.00503

Gnomad ASJ exome AF: 0.00466

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.0000463

Gnomad NFE exome AF: 0.00158

Gnomad OTH exome AF: 0.00620

GnomAD4 exome AF: 0.00356 AC: 5205 AN: 1460056 Hom.: 174 Cov.: 30 AF XY: 0.00317 AC XY: 2299 AN XY: 726336

African (AFR) AF: 0.0962 AC: 3214 AN: 33424

American (AMR) AF: 0.00581 AC: 260 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00497 AC: 130 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000894 AC: 77 AN: 86176

European-Finnish (FIN) AF: 0.0000937 AC: 5 AN: 53386

Middle Eastern (MID) AF: 0.0158 AC: 70 AN: 4424

European-Non Finnish (NFE) AF: 0.000884 AC: 983 AN: 1111864

Other (OTH) AF: 0.00774 AC: 466 AN: 60232

GnomAD4 genome AF: 0.0266 AC: 4050 AN: 152290 Hom.: 169 Cov.: 33 AF XY: 0.0249 AC XY: 1853 AN XY: 74454

African (AFR) AF: 0.0902 AC: 3749 AN: 41550

American (AMR) AF: 0.00849 AC: 130 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00634 AC: 22 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00166 AC: 8 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00143 AC: 97 AN: 68018

Other (OTH) AF: 0.0194 AC: 41 AN: 2114

Alfa AF: 0.0109 Hom.: 86

Bravo AF: 0.0298

Asia WGS AF: 0.00404 AC: 14 AN: 3478

EpiCase AF: 0.00196

EpiControl AF: 0.00267

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.0070
DANN	Benign	0.29
PhyloP100		-4.0
Mutation Taster		=99/1	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: rs2230761; hg19: chr7-48146639;