rs3219467

chr1-45340144-G-Cchr1-45340144-G-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000372098.7(MUTYH):c.36+75C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00294 in 1,584,652 control chromosomes in the GnomAD database, including 16 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 0.0022 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0030 (16 hom.)
• Consequence: MUTYH ENST00000372098.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0940

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]

TOE1 (HGNC:15954): (target of EGR1, exonuclease) Enables poly(A)-specific ribonuclease activity and snRNA binding activity. Involved in RNA phosphodiester bond hydrolysis, exonucleolytic and snRNA 3'-end processing. Located in Cajal body and cytoplasm. Implicated in pontocerebellar hypoplasia type 7. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUTYH	NM_001128425.2	c.36+75C>G		intron_variant		ENST00000710952.2
TOE1	NM_025077.4			upstream_gene_variant		ENST00000372090.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUTYH	ENST00000710952.2	c.36+75C>G		intron_variant			NM_001128425.2
TOE1	ENST00000372090.6			upstream_gene_variant		1	NM_025077.4	P1

Frequencies

GnomAD3 genomes AF: 0.00217 AC: 331 AN: 152184 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000772

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00393

Gnomad FIN AF: 0.00330

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00323

Gnomad OTH AF: 0.00287

GnomAD4 exome AF: 0.00303 AC: 4334 AN: 1432350 Hom.: 16 Cov.: 33 AF XY: 0.00303 AC XY: 2149 AN XY: 710218

Gnomad4 AFR exome AF: 0.000337

Gnomad4 AMR exome AF: 0.00102

Gnomad4 ASJ exome AF: 0.000235

Gnomad4 EAS exome AF: 0.0000266

Gnomad4 SAS exome AF: 0.00395

Gnomad4 FIN exome AF: 0.00226

Gnomad4 NFE exome AF: 0.00335

Gnomad4 OTH exome AF: 0.00235

GnomAD4 genome AF: 0.00217 AC: 330 AN: 152302 Hom.: 0 Cov.: 32 AF XY: 0.00234 AC XY: 174 AN XY: 74478

Gnomad4 AFR AF: 0.000770

Gnomad4 AMR AF: 0.00111

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00373

Gnomad4 FIN AF: 0.00330

Gnomad4 NFE AF: 0.00323

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.000952 Hom.: 0

Bravo AF: 0.00187

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	4.2
Dann	Benign	0.74

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: rs3219467; hg19: chr1-45805816; COSMIC: COSV104536723; COSMIC: COSV104536723;