Variant 1-45338378-C-T 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+1521G>A variant causes a intron 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_001048174.2 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0170

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=-0.88).

BP6

Variant 1-45338378-C-T is Benign according to our data. Variant chr1-45338378-C-T is described in ClinVar as [Benign]. Clinvar id is 1260538.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.392 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+1521G>A		intron_variant		ENST00000456914.7
MUTYH	NM_001128425.2 linkuse as main transcript	c.36+1841G>A		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+1521G>A		intron_variant		1	NM_001048174.2	A1	Q9UIF7-6
MUTYH	ENST00000710952.2 linkuse as main transcript	c.36+1841G>A		intron_variant			NM_001128425.2

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

Gnomad4 AFR exome

AF:

0.244

Gnomad4 AMR exome

AF:

0.452

Gnomad4 ASJ exome

AF:

0.254

Gnomad4 EAS exome

AF:

0.350

Gnomad4 SAS exome

AF:

0.227

Gnomad4 FIN exome

AF:

0.221

Gnomad4 NFE exome

AF:

0.237

Gnomad4 OTH exome

AF:

0.266

GnomAD4 genome

AF:

0.263

AC:

40035

AN:

152170

Hom.:

5580

Cov.:

AF XY:

0.263

AC XY:

19535

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.249

Gnomad4 AMR

AF:

0.400

Gnomad4 ASJ

AF:

0.260

Gnomad4 EAS

AF:

0.365

Gnomad4 SAS

AF:

0.233

Gnomad4 FIN

AF:

0.208

Gnomad4 NFE

AF:

0.242

Gnomad4 OTH

AF:

0.298

Alfa

AF:

0.255

Hom.:

8751

Bravo

AF:

0.280

Asia WGS

AF:

0.339

AC:

1177

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 22, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

3.9

DANN

Benign

0.64

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