rs3219474

Positions:

• chr1-45337741-A-G

Variant summary

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

The NM_001048174.2(MUTYH):​c.-7+2158T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0557 in 152,042 control chromosomes in the GnomAD database, including 285 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 0.056 (285 hom., cov: 31)
• Consequence: MUTYH NM_001048174.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.320

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]

ENSG00000288208 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0761 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUTYH	NM_001048174.2	c.-7+2158T>C		intron_variant		ENST00000456914.7	NP_001041639.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUTYH	ENST00000456914.7	c.-7+2158T>C		intron_variant		1	NM_001048174.2	ENSP00000407590.2
ENSG00000288208	ENST00000671898.1	n.541-3230T>C		intron_variant				ENSP00000499896.1

Frequencies

GnomAD3 genomes AF: 0.0558 AC: 8470 AN: 151924 Hom.: 285 Cov.: 31

Gnomad AFR AF: 0.0307

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.0411

Gnomad ASJ AF: 0.0804

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0697

Gnomad FIN AF: 0.0453

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0779

Gnomad OTH AF: 0.0608

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

GnomAD4 genome AF: 0.0557 AC: 8467 AN: 152042 Hom.: 285 Cov.: 31 AF XY: 0.0544 AC XY: 4046 AN XY: 74334

Gnomad4 AFR AF: 0.0306

Gnomad4 AMR AF: 0.0410

Gnomad4 ASJ AF: 0.0804

Gnomad4 EAS AF: 0.000580

Gnomad4 SAS AF: 0.0696

Gnomad4 FIN AF: 0.0453

Gnomad4 NFE AF: 0.0779

Gnomad4 OTH AF: 0.0602

Alfa AF: 0.0741 Hom.: 583

Bravo AF: 0.0538

Asia WGS AF: 0.0260 AC: 90 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.5
DANN	Benign	0.54

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: rs3219474; hg19: chr1-45803413;