rs3219495

Variant names:

• chr1-45330443-G-A
• rs3219495
• NM_001048174.2:c.1434+73C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-45330443-G-A
• chr1-45330443-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.212
• Publications: 5 publications found

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 Gene-Disease associations (from GenCC):

• familial adenomatous polyposis 2

  Inheritance: AD, AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, ClinGen, G2P
• colorectal cancer

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
• familial ovarian cancer

  Inheritance: AD, AR Classification: NO_KNOWN Submitted by: ClinGen
• hereditary breast carcinoma

  Inheritance: AD, AR Classification: NO_KNOWN Submitted by: ClinGen

ENSG00000288208 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 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 VariationId is 1260412.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
MUTYH	NM_001048174.2	c.1434+73C>T		intron_variant	Intron 15 of 15	ENST00000456914.7	NP_001041639.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUTYH	ENST00000456914.7	c.1434+73C>T		intron_variant	Intron 15 of 15	1	NM_001048174.2	ENSP00000407590.2
ENSG00000288208	ENST00000671898.1	n.2022+73C>T		intron_variant	Intron 19 of 20			ENSP00000499896.1

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

African (AFR) AF: 0.237 AC: 7109 AN: 29936

American (AMR) AF: 0.0140 AC: 526 AN: 37478

Ashkenazi Jewish (ASJ) AF: 0.000122 AC: 3 AN: 24674

East Asian (EAS) AF: 0.0000276 AC: 1 AN: 36284

South Asian (SAS) AF: 0.000497 AC: 39 AN: 78404

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50362

Middle Eastern (MID) AF: 0.00724 AC: 40 AN: 5526

European-Non Finnish (NFE) AF: 0.000319 AC: 319 AN: 1001010

Other (OTH) AF: 0.0147 AC: 814 AN: 55384

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

African (AFR) AF: 0.231 AC: 9532 AN: 41326

American (AMR) AF: 0.0262 AC: 400 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5156

South Asian (SAS) AF: 0.00125 AC: 6 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10568

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.000529 AC: 36 AN: 68002

Other (OTH) AF: 0.0417 AC: 88 AN: 2112

Alfa AF: 0.0129 Hom.: 171

Bravo AF: 0.0755

Asia WGS AF: 0.0120 AC: 42 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.9
DANN	Benign	0.45
PhyloP100		-0.21
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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