Variant 1-45330597-G-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.1393-40C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.914 in 1,590,222 control chromosomes in the GnomAD database, including 664,951 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.93 ( 65876 hom., cov: 32)

Exomes 𝑓: 0.91 ( 599075 hom. )

Consequence

MUTYH
NM_001048174.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.263

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BP6

Variant 1-45330597-G-C is Benign according to our data. Variant chr1-45330597-G-C is described in ClinVar as [Benign]. Clinvar id is 439920.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-45330597-G-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.949 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.1393-40C>G		intron_variant		ENST00000456914.7	NP_001041639.1
MUTYH	NM_001128425.2 linkuse as main transcript	c.1477-40C>G		intron_variant		ENST00000710952.2	NP_001121897.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUTYH	ENST00000456914.7 linkuse as main transcript	c.1393-40C>G		intron_variant		1	NM_001048174.2	ENSP00000407590	A1	Q9UIF7-6
MUTYH	ENST00000710952.2 linkuse as main transcript	c.1477-40C>G		intron_variant			NM_001128425.2	ENSP00000518552

Frequencies

GnomAD3 genomes

AF:

0.929

AC:

141427

AN:

152158

Hom.:

65830

Cov.:

show subpopulations

Gnomad AFR

AF:

0.957

Gnomad AMI

AF:

0.894

Gnomad AMR

AF:

0.929

Gnomad ASJ

AF:

0.887

Gnomad EAS

AF:

0.900

Gnomad SAS

AF:

0.926

Gnomad FIN

AF:

0.977

Gnomad MID

AF:

0.896

Gnomad NFE

AF:

0.911

Gnomad OTH

AF:

0.918

GnomAD3 exomes

AF:

0.925

AC:

199278

AN:

215550

Hom.:

92168

AF XY:

0.922

AC XY:

106752

AN XY:

115768

show subpopulations

Gnomad AFR exome

AF:

0.959

Gnomad AMR exome

AF:

0.951

Gnomad ASJ exome

AF:

0.884

Gnomad EAS exome

AF:

0.891

Gnomad SAS exome

AF:

0.918

Gnomad FIN exome

AF:

0.978

Gnomad NFE exome

AF:

0.912

Gnomad OTH exome

AF:

0.920

GnomAD4 exome

AF:

0.913

AC:

1312359

AN:

1437946

Hom.:

599075

Cov.:

AF XY:

0.912

AC XY:

650648

AN XY:

713204

show subpopulations

Gnomad4 AFR exome

AF:

0.958

Gnomad4 AMR exome

AF:

0.948

Gnomad4 ASJ exome

AF:

0.892

Gnomad4 EAS exome

AF:

0.883

Gnomad4 SAS exome

AF:

0.916

Gnomad4 FIN exome

AF:

0.975

Gnomad4 NFE exome

AF:

0.908

Gnomad4 OTH exome

AF:

0.917

GnomAD4 genome

AF:

0.929

AC:

141531

AN:

152276

Hom.:

65876

Cov.:

AF XY:

0.933

AC XY:

69491

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.957

Gnomad4 AMR

AF:

0.929

Gnomad4 ASJ

AF:

0.887

Gnomad4 EAS

AF:

0.900

Gnomad4 SAS

AF:

0.926

Gnomad4 FIN

AF:

0.977

Gnomad4 NFE

AF:

0.911

Gnomad4 OTH

AF:

0.919

Alfa

AF:

0.921

Hom.:

11932

Bravo

AF:

0.926

Asia WGS

AF:

0.922

AC:

3207

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Mar 30, 2020	- -

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

-0.96

CADD

Benign

7.9

DANN

Benign

0.46

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