rs3219495

chr1-45330443-G-Achr1-45330443-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001048174.2(MUTYH):c.1434+73C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0129 in 1,470,990 control chromosomes in the GnomAD database, including 2,054 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.066 (1173 hom., cov: 30)
  • Exomes 𝑓: 0.0067 (881 hom.)
• Consequence: MUTYH NM_001048174.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.212

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 1-45330443-G-A is Benign according to our data. Variant chr1-45330443-G-A is described in ClinVar as [Benign]. Clinvar id is 1260412.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.227 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUTYH	NM_001048174.2	c.1434+73C>T		intron_variant		ENST00000456914.7
MUTYH	NM_001128425.2	c.1518+73C>T		intron_variant		ENST00000710952.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUTYH	ENST00000456914.7	c.1434+73C>T		intron_variant		1	NM_001048174.2	A1
MUTYH	ENST00000710952.2	c.1518+73C>T		intron_variant			NM_001128425.2

Frequencies

GnomAD3 genomes AF: 0.0663 AC: 10068 AN: 151814 Hom.: 1174 Cov.: 30

Gnomad AFR AF: 0.231

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.000544

Gnomad OTH AF: 0.0421

GnomAD4 exome AF: 0.00671 AC: 8851 AN: 1319058 Hom.: 881 AF XY: 0.00584 AC XY: 3838 AN XY: 657010

Gnomad4 AFR exome AF: 0.237

Gnomad4 AMR exome AF: 0.0140

Gnomad4 ASJ exome AF: 0.000122

Gnomad4 EAS exome AF: 0.0000276

Gnomad4 SAS exome AF: 0.000497

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000319

Gnomad4 OTH exome AF: 0.0147

GnomAD4 genome AF: 0.0663 AC: 10068 AN: 151932 Hom.: 1173 Cov.: 30 AF XY: 0.0647 AC XY: 4802 AN XY: 74254

Gnomad4 AFR AF: 0.231

Gnomad4 AMR AF: 0.0262

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00125

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000529

Gnomad4 OTH AF: 0.0417

Alfa AF: 0.0110 Hom.: 82

Bravo AF: 0.0755

Asia WGS AF: 0.0120 AC: 42 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	2.9
Dann	Benign	0.45

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

Other links and lift over

dbSNP: rs3219495; hg19: chr1-45796115; COSMIC: COSV104641836; COSMIC: COSV104641836;