1-45340203-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_025077.4(TOE1):​c.-50C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,268 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TOE1
NM_025077.4 5_prime_UTR

Scores

2
Splicing: ADA: 0.03721
2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.26
Variant links:
Genes affected
TOE1 (HGNC:15954): (target of EGR1, exonuclease) Enables poly(A)-specific ribonuclease activity and snRNA binding activity. Involved in RNA phosphodiester bond hydrolysis, exonucleolytic and snRNA 3'-end processing. Located in Cajal body and cytoplasm. Implicated in pontocerebellar hypoplasia type 7. [provided by Alliance of Genome Resources, Apr 2022]
MUTYH (HGNC:7527): (mutY DNA glycosylase) This gene encodes a DNA glycosylase involved in oxidative DNA damage repair. The enzyme excises adenine bases from the DNA backbone at sites where adenine is inappropriately paired with guanine, cytosine, or 8-oxo-7,8-dihydroguanine, a major oxidatively damaged DNA lesion. The protein is localized to the nucleus and mitochondria. This gene product is thought to play a role in signaling apoptosis by the introduction of single-strand breaks following oxidative damage. Mutations in this gene result in heritable predisposition to colorectal cancer, termed MUTYH-associated polyposis (MAP). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2017]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.39).
BP6
Variant 1-45340203-C-G is Benign according to our data. Variant chr1-45340203-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2802506.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TOE1NM_025077.4 linkuse as main transcriptc.-50C>G 5_prime_UTR_variant 1/8 ENST00000372090.6
MUTYHNM_001128425.2 linkuse as main transcriptc.36+16G>C intron_variant ENST00000710952.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TOE1ENST00000372090.6 linkuse as main transcriptc.-50C>G 5_prime_UTR_variant 1/81 NM_025077.4 P1Q96GM8-1
MUTYHENST00000710952.2 linkuse as main transcriptc.36+16G>C intron_variant NM_001128425.2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000402
AC:
1
AN:
248788
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135164
show subpopulations
Gnomad AFR exome
AF:
0.0000629
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461268
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
726960
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Familial adenomatous polyposis 2 Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeNov 17, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.39
CADD
Benign
18
DANN
Benign
0.86

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.037
dbscSNV1_RF
Benign
0.27
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs748512468; hg19: chr1-45805875; API