Variant 1-45339894-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001048174.2(MUTYH):c.-7+5C>G variant causes a splice donor 5th base, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.988 in 1,401,720 control chromosomes in the GnomAD database, including 683,553 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.99 ( 74671 hom., cov: 31)

Exomes 𝑓: 0.99 ( 608882 hom. )

Consequence

MUTYH
NM_001048174.2 splice_donor_5th_base, intron

Scores

Splicing: ADA: 0.00004900

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: -2.00

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 1-45339894-G-C is Benign according to our data. Variant chr1-45339894-G-C is described in ClinVar as [Benign]. Clinvar id is 1244445.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45339894-G-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.989 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUTYH	NM_001048174.2 linkuse as main transcript	c.-7+5C>G		splice_donor_5th_base_variant, intron_variant		ENST00000456914.7
MUTYH	NM_001128425.2 linkuse as main transcript	c.36+325C>G		intron_variant		ENST00000710952.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUTYH	ENST00000456914.7 linkuse as main transcript	c.-7+5C>G		splice_donor_5th_base_variant, intron_variant		1	NM_001048174.2	A1	Q9UIF7-6
MUTYH	ENST00000710952.2 linkuse as main transcript	c.36+325C>G		intron_variant			NM_001128425.2

Frequencies

GnomAD3 genomes

AF:

0.990

AC:

150678

AN:

152156

Hom.:

74611

Cov.:

show subpopulations

Gnomad AFR

AF:

0.997

Gnomad AMI

AF:

0.987

Gnomad AMR

AF:

0.988

Gnomad ASJ

AF:

0.994

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.997

Gnomad FIN

AF:

0.994

Gnomad MID

AF:

0.991

Gnomad NFE

AF:

0.985

Gnomad OTH

AF:

0.989

GnomAD3 exomes

AF:

0.990

AC:

168681

AN:

170428

Hom.:

83479

AF XY:

0.990

AC XY:

91806

AN XY:

92742

show subpopulations

Gnomad AFR exome

AF:

0.997

Gnomad AMR exome

AF:

0.991

Gnomad ASJ exome

AF:

0.994

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

0.996

Gnomad FIN exome

AF:

0.991

Gnomad NFE exome

AF:

0.984

Gnomad OTH exome

AF:

0.986

GnomAD4 exome

AF:

0.987

AC:

1233495

AN:

1249446

Hom.:

608882

Cov.:

AF XY:

0.987

AC XY:

606722

AN XY:

614462

show subpopulations

Gnomad4 AFR exome

AF:

0.998

Gnomad4 AMR exome

AF:

0.991

Gnomad4 ASJ exome

AF:

0.995

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.996

Gnomad4 FIN exome

AF:

0.991

Gnomad4 NFE exome

AF:

0.985

Gnomad4 OTH exome

AF:

0.989

GnomAD4 genome

AF:

0.990

AC:

150797

AN:

152274

Hom.:

74671

Cov.:

AF XY:

0.991

AC XY:

73822

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.997

Gnomad4 AMR

AF:

0.988

Gnomad4 ASJ

AF:

0.994

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

0.997

Gnomad4 FIN

AF:

0.994

Gnomad4 NFE

AF:

0.985

Gnomad4 OTH

AF:

0.989

Alfa

AF:

0.985

Hom.:

7779

Bravo

AF:

0.990

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Hereditary cancer-predisposing syndrome

Benign:1

Benign, no assertion criteria provided

clinical testing

Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.

Dec 21, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

Cadd

Benign

0.25

Dann

Benign

0.50

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000049

dbscSNV1_RF

Benign

0.0020

SpliceAI score (max)

0.10

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