Variant 1-45332883-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001048174.2(MUTYH):c.420+35A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.916 in 1,614,088 control chromosomes in the GnomAD database, including 677,042 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.93 ( 66325 hom., cov: 31)

Exomes 𝑓: 0.91 ( 610717 hom. )

Consequence

MUTYH
NM_001048174.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.26

Variant links:

Genes affected

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]

MUTYH links:

ENSG00000288208 (HGNC:):

ENSG00000288208 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 1-45332883-T-C is Benign according to our data. Variant chr1-45332883-T-C is described in ClinVar as [Benign]. Clinvar id is 257529.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-45332883-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.958 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUTYH	NM_001048174.2 linkuse as main transcript	c.420+35A>G		intron_variant		ENST00000456914.7	NP_001041639.1	Q9UIF7-6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUTYH	ENST00000456914.7 linkuse as main transcript	c.420+35A>G		intron_variant		1	NM_001048174.2	ENSP00000407590.2		Q9UIF7-6
ENSG00000288208	ENST00000671898.1 linkuse as main transcript	n.1008+35A>G		intron_variant				ENSP00000499896.1		A0A5F9ZGZ0

Frequencies

GnomAD3 genomes

AF:

0.933

AC:

141872

AN:

152118

Hom.:

66268

Cov.:

show subpopulations

Gnomad AFR

AF:

0.966

Gnomad AMI

AF:

0.893

Gnomad AMR

AF:

0.932

Gnomad ASJ

AF:

0.893

Gnomad EAS

AF:

0.901

Gnomad SAS

AF:

0.928

Gnomad FIN

AF:

0.977

Gnomad MID

AF:

0.896

Gnomad NFE

AF:

0.912

Gnomad OTH

AF:

0.919

GnomAD3 exomes

AF:

0.926

AC:

232563

AN:

251096

Hom.:

107789

AF XY:

0.924

AC XY:

125367

AN XY:

135726

show subpopulations

Gnomad AFR exome

AF:

0.968

Gnomad AMR exome

AF:

0.953

Gnomad ASJ exome

AF:

0.891

Gnomad EAS exome

AF:

0.890

Gnomad SAS exome

AF:

0.919

Gnomad FIN exome

AF:

0.978

Gnomad NFE exome

AF:

0.913

Gnomad OTH exome

AF:

0.921

GnomAD4 exome

AF:

0.914

AC:

1335987

AN:

1461852

Hom.:

610717

Cov.:

AF XY:

0.914

AC XY:

664326

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.969

Gnomad4 AMR exome

AF:

0.949

Gnomad4 ASJ exome

AF:

0.899

Gnomad4 EAS exome

AF:

0.883

Gnomad4 SAS exome

AF:

0.918

Gnomad4 FIN exome

AF:

0.975

Gnomad4 NFE exome

AF:

0.909

Gnomad4 OTH exome

AF:

0.920

GnomAD4 genome

AF:

0.933

AC:

141987

AN:

152236

Hom.:

66325

Cov.:

AF XY:

0.936

AC XY:

69686

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.966

Gnomad4 AMR

AF:

0.932

Gnomad4 ASJ

AF:

0.893

Gnomad4 EAS

AF:

0.900

Gnomad4 SAS

AF:

0.928

Gnomad4 FIN

AF:

0.977

Gnomad4 NFE

AF:

0.911

Gnomad4 OTH

AF:

0.920

Alfa

AF:

0.913

Hom.:

86088

Bravo

AF:

0.930

Asia WGS

AF:

0.925

AC:

3217

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Apr 10, 2020	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Familial adenomatous polyposis 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Jul 07, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.61

DANN

Benign

0.41

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over