rs3219476

Positions:

• chr1-45336998-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001048174.2(MUTYH):​c.-6-2487T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.577 in 151,826 control chromosomes in the GnomAD database, including 26,647 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.58 (26647 hom., cov: 30)
• Consequence: MUTYH NM_001048174.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.178

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.666 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUTYH	NM_001048174.2	c.-6-2487T>G		intron_variant		ENST00000456914.7
MUTYH	NM_001128425.2	c.37-2487T>G		intron_variant		ENST00000710952.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUTYH	ENST00000456914.7	c.-6-2487T>G		intron_variant		1	NM_001048174.2	A1
MUTYH	ENST00000710952.2	c.37-2487T>G		intron_variant			NM_001128425.2

Frequencies

GnomAD3 genomes AF: 0.578 AC: 87618 AN: 151706 Hom.: 26646 Cov.: 30

Gnomad AFR AF: 0.404

Gnomad AMI AF: 0.621

Gnomad AMR AF: 0.497

Gnomad ASJ AF: 0.624

Gnomad EAS AF: 0.505

Gnomad SAS AF: 0.685

Gnomad FIN AF: 0.763

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.668

Gnomad OTH AF: 0.569

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.577 AC: 87630 AN: 151826 Hom.: 26647 Cov.: 30 AF XY: 0.583 AC XY: 43279 AN XY: 74222

Gnomad4 AFR AF: 0.404

Gnomad4 AMR AF: 0.496

Gnomad4 ASJ AF: 0.624

Gnomad4 EAS AF: 0.504

Gnomad4 SAS AF: 0.686

Gnomad4 FIN AF: 0.763

Gnomad4 NFE AF: 0.668

Gnomad4 OTH AF: 0.563

Alfa AF: 0.643 Hom.: 14840

Bravo AF: 0.545

Asia WGS AF: 0.549 AC: 1907 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.0
DANN	Benign	0.36

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: rs3219476; hg19: chr1-45802670;