rs3219472

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001407087.1(MUTYH):c.-181G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 461,784 control chromosomes in the GnomAD database, including 16,857 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 5580 hom., cov: 32)

Exomes 𝑓: 0.26 ( 11277 hom. )

Consequence

MUTYH
NM_001407087.1 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0170

Publications

20 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: G2P, Labcorp Genetics (formerly Invitae), ClinGen, Genomics England PanelApp, 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

new If you want to explore the variant's impact on the transcript NM_001407087.1, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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 1-45338378-C-T is Benign according to our data. Variant chr1-45338378-C-T is described in ClinVar as Benign. ClinVar VariationId is 1260538.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001407087.1. 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.36+1841G>A	intron	N/A	NP_001121897.1	E5KP25
MUTYH	NM_001048174.2	MANE Select	c.-7+1521G>A	intron	N/A	NP_001041639.1	Q9UIF7-6
MUTYH	NM_001407087.1		c.-181G>A	5_prime_UTR	Exon 2 of 17	NP_001394016.1	A0AAQ5BGW7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MUTYH	ENST00000710952.2	MANE Plus Clinical	c.36+1841G>A	intron	N/A	ENSP00000518552.2	E5KP25
MUTYH	ENST00000456914.7	TSL:1 MANE Select	c.-7+1521G>A	intron	N/A	ENSP00000407590.2	Q9UIF7-6
MUTYH	ENST00000372098.7	TSL:1	c.36+1841G>A	intron	N/A	ENSP00000361170.3	Q9UIF7-1

Frequencies

GnomAD3 genomes

AF:

0.263

AC:

39986

AN:

152052

Hom.:

5557

Cov.:

show subpopulations

Gnomad AFR

AF:

0.250

Gnomad AMI

AF:

0.273

Gnomad AMR

AF:

0.399

Gnomad ASJ

AF:

0.260

Gnomad EAS

AF:

0.365

Gnomad SAS

AF:

0.233

Gnomad FIN

AF:

0.208

Gnomad MID

AF:

0.269

Gnomad NFE

AF:

0.242

Gnomad OTH

AF:

0.293

GnomAD4 exome

AF:

0.259

AC:

80163

AN:

309614

Hom.:

11277

Cov.:

AF XY:

0.252

AC XY:

41705

AN XY:

165284

show subpopulations

African (AFR)

AF:

0.244

AC:

2528

AN:

10380

American (AMR)

AF:

0.452

AC:

9247

AN:

20458

Ashkenazi Jewish (ASJ)

AF:

0.254

AC:

2782

AN:

10960

East Asian (EAS)

AF:

0.350

AC:

6898

AN:

19712

South Asian (SAS)

AF:

0.227

AC:

11313

AN:

49826

European-Finnish (FIN)

AF:

0.221

AC:

2121

AN:

9616

Middle Eastern (MID)

AF:

0.271

AC:

349

AN:

1286

European-Non Finnish (NFE)

AF:

0.237

AC:

40286

AN:

169942

Other (OTH)

AF:

0.266

AC:

4639

AN:

17434

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

2803

5606

8410

11213

14016

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

336

672

1008

1344

1680

<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:

0.263

AC:

40035

AN:

152170

Hom.:

5580

Cov.:

AF XY:

0.263

AC XY:

19535

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.249

AC:

10352

AN:

41504

American (AMR)

AF:

0.400

AC:

6128

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.260

AC:

902

AN:

3470

East Asian (EAS)

AF:

0.365

AC:

1889

AN:

5178

South Asian (SAS)

AF:

0.233

AC:

1123

AN:

4824

European-Finnish (FIN)

AF:

0.208

AC:

2203

AN:

10590

Middle Eastern (MID)

AF:

0.272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.242

AC:

16478

AN:

67978

Other (OTH)

AF:

0.298

AC:

631

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1486

2972

4457

5943

7429

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

414

828

1242

1656

2070

<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:

0.257

Hom.:

14284

Bravo

AF:

0.280

Asia WGS

AF:

0.339

AC:

1177

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

3.9

(source)

DANN

Benign

0.64

PhyloP100

0.017

Mutation Taster

=100/0

polymorphism (auto)

(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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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