1-45331583-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBS2_Supporting

The NM_001048174.2(MUTYH):c.1103-27C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00425 in 1,613,578 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0030 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0044 ( 17 hom. )

Consequence

MUTYH
NM_001048174.2 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.676

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 1-45331583-G-A is Benign according to our data. Variant chr1-45331583-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 801475.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-45331583-G-A is described in Lovd as [Benign].

BS2

High Homozygotes in GnomAdExome4 at 17 AR geneVariant has number of homozygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUTYH	NM_001048174.2 link	c.1103-27C>T		intron_variant	Intron 12 of 15	ENST00000456914.7	NP_001041639.1	Q9UIF7-6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUTYH	ENST00000456914.7 link	c.1103-27C>T		intron_variant	Intron 12 of 15	1	NM_001048174.2	ENSP00000407590.2		Q9UIF7-6
ENSG00000288208	ENST00000671898.1 link	n.1691-27C>T		intron_variant	Intron 16 of 20			ENSP00000499896.1		A0A5F9ZGZ0

Frequencies

GnomAD3 genomes

AF:

0.00300

AC:

456

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00104

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00268

Gnomad ASJ

AF:

0.00375

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00492

Gnomad OTH

AF:

0.00621

GnomAD2 exomes

AF:

0.00365

AC:

908

AN:

248612

AF XY:

0.00380

show subpopulations

Gnomad AFR exome

AF:

0.00109

Gnomad AMR exome

AF:

0.00301

Gnomad ASJ exome

AF:

0.00379

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000525

Gnomad NFE exome

AF:

0.00577

Gnomad OTH exome

AF:

0.00280

GnomAD4 exome

AF:

0.00438

AC:

6406

AN:

1461218

Hom.:

Cov.:

AF XY:

0.00443

AC XY:

3222

AN XY:

726876

show subpopulations

Gnomad4 AFR exome

AF:

0.000597

AC:

AN:

33480

Gnomad4 AMR exome

AF:

0.00295

AC:

132

AN:

44722

Gnomad4 ASJ exome

AF:

0.00363

AC:

AN:

26136

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

39700

Gnomad4 SAS exome

AF:

0.00242

AC:

209

AN:

86258

Gnomad4 FIN exome

AF:

0.000455

AC:

AN:

52782

Gnomad4 NFE exome

AF:

0.00506

AC:

5626

AN:

1111986

Gnomad4 Remaining exome

AF:

0.00439

AC:

265

AN:

60386

Heterozygous variant carriers

439

878

1317

1756

2195

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

200

400

600

800

1000

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00299

AC:

456

AN:

152360

Hom.:

Cov.:

AF XY:

0.00281

AC XY:

209

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.00103

AC:

0.00103395

AN:

0.00103395

Gnomad4 AMR

AF:

0.00268

AC:

0.00267799

AN:

0.00267799

Gnomad4 ASJ

AF:

0.00375

AC:

0.00375072

AN:

0.00375072

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.00186

AC:

0.0018649

AN:

0.0018649

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.00492

AC:

0.00492386

AN:

0.00492386

Gnomad4 OTH

AF:

0.00614

AC:

0.00614367

AN:

0.00614367

Heterozygous variant carriers

102

128

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00447

Hom.:

Bravo

AF:

0.00320

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Apr 10, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

MUTYH: BS1, BS2 -

Jun 24, 2019

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 17949294, 15943555, 17524638, 16774938, 16616356, 16557584, 22297469, 20191381, 21777424, 27829682) -

Familial adenomatous polyposis 2

Benign:2

May 28, 2019

Mendelics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 20, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Mar 04, 2025

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

MUTYH-related disorder

Benign:1

Dec 02, 2021

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Hereditary cancer-predisposing syndrome

Benign:1

Jul 29, 2021

Sema4, Sema4

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:curation

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

4.5

DANN

Benign

0.55

Mutation Taster

=100/0

polymorphism

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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