chr1-45332883-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -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:6

Conservation

PhyloP100: -1.26

Publications

45 publications found

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 Gene-Disease associations (from GenCC):

familial adenomatous polyposis 2
Inheritance: AR, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), ClinGen, G2P, Orphanet
colorectal cancer
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
familial ovarian cancer
Inheritance: AD, AR Classification: NO_KNOWN Submitted by: ClinGen
hereditary breast carcinoma
Inheritance: AR, AD Classification: NO_KNOWN Submitted by: ClinGen

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 -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 VariationId is 257529.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001048174.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MUTYH	NM_001128425.2	MANE Plus Clinical	c.504+35A>G	intron	N/A	NP_001121897.1	E5KP25
MUTYH	NM_001048174.2	MANE Select	c.420+35A>G	intron	N/A	NP_001041639.1	Q9UIF7-6
MUTYH	NM_012222.3		c.495+35A>G	intron	N/A	NP_036354.1	Q9UIF7-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MUTYH	ENST00000710952.2	MANE Plus Clinical	c.504+35A>G	intron	N/A	ENSP00000518552.2	E5KP25
MUTYH	ENST00000456914.7	TSL:1 MANE Select	c.420+35A>G	intron	N/A	ENSP00000407590.2	Q9UIF7-6
MUTYH	ENST00000372098.7	TSL:1	c.495+35A>G	intron	N/A	ENSP00000361170.3	Q9UIF7-1

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

GnomAD2 exomes

AF:

0.926

AC:

232563

AN:

251096

AF XY:

0.924

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 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

African (AFR)

AF:

0.969

AC:

32433

AN:

33480

American (AMR)

AF:

0.949

AC:

42464

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.899

AC:

23487

AN:

26136

East Asian (EAS)

AF:

0.883

AC:

35052

AN:

39700

South Asian (SAS)

AF:

0.918

AC:

79175

AN:

86258

European-Finnish (FIN)

AF:

0.975

AC:

52059

AN:

53416

Middle Eastern (MID)

AF:

0.919

AC:

5299

AN:

5768

European-Non Finnish (NFE)

AF:

0.909

AC:

1010485

AN:

1111976

Other (OTH)

AF:

0.920

AC:

55533

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

7779

15558

23338

31117

38896

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21486

42972

64458

85944

107430

<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:

0.933

AC:

141987

AN:

152236

Hom.:

66325

Cov.:

AF XY:

0.936

AC XY:

69686

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.966

AC:

40128

AN:

41546

American (AMR)

AF:

0.932

AC:

14261

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.893

AC:

3099

AN:

3470

East Asian (EAS)

AF:

0.900

AC:

4658

AN:

5176

South Asian (SAS)

AF:

0.928

AC:

4470

AN:

4818

European-Finnish (FIN)

AF:

0.977

AC:

10374

AN:

10616

Middle Eastern (MID)

AF:

0.895

AC:

263

AN:

294

European-Non Finnish (NFE)

AF:

0.911

AC:

61979

AN:

67998

Other (OTH)

AF:

0.920

AC:

1942

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

503

1006

1509

2012

2515

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

910

1820

2730

3640

4550

<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:

0.919

Hom.:

125881

Bravo

AF:

0.930

Asia WGS

AF:

0.925

AC:

3217

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Familial adenomatous polyposis 2 (1)

Hereditary cancer-predisposing syndrome (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.61

(source)

DANN

Benign

0.41

PhyloP100

-1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=4/96

disease causing

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over