Variant 8-127736331-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_002467.6(MYC):c.-263G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00149 in 591,304 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0012 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0016 ( 1 hom. )

Consequence

MYC
NM_002467.6 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.24

Variant links:

Genes affected

MYC (HGNC:7553): (MYC proto-oncogene, bHLH transcription factor) This gene is a proto-oncogene and encodes a nuclear phosphoprotein that plays a role in cell cycle progression, apoptosis and cellular transformation. The encoded protein forms a heterodimer with the related transcription factor MAX. This complex binds to the E box DNA consensus sequence and regulates the transcription of specific target genes. Amplification of this gene is frequently observed in numerous human cancers. Translocations involving this gene are associated with Burkitt lymphoma and multiple myeloma in human patients. There is evidence to show that translation initiates both from an upstream, in-frame non-AUG (CUG) and a downstream AUG start site, resulting in the production of two isoforms with distinct N-termini. [provided by RefSeq, Aug 2017]

MYC links:

CASC11 (HGNC:48939): (cancer susceptibility 11)

CASC11 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.028512686).

BP6

Variant 8-127736331-G-A is Benign according to our data. Variant chr8-127736331-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2658810.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 179 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYC	NM_002467.6 linkuse as main transcript	c.-263G>A		5_prime_UTR_variant	1/3	ENST00000621592.8	NP_002458.2
MYC	NM_001354870.1 linkuse as main transcript	c.-263G>A		5_prime_UTR_variant	1/3		NP_001341799.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYC	ENST00000621592.8 linkuse as main transcript	c.-263G>A		5_prime_UTR_variant	1/3	1	NM_002467.6	ENSP00000478887	A2	P01106-2

Frequencies

GnomAD3 genomes

AF:

0.00118

AC:

179

AN:

152248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00403

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000413

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00213

Gnomad OTH

AF:

0.000478

GnomAD4 exome

AF:

0.00160

AC:

704

AN:

438938

Hom.:

Cov.:

AF XY:

0.00164

AC XY:

379

AN XY:

230774

show subpopulations

Gnomad4 AFR exome

AF:

0.000165

Gnomad4 AMR exome

AF:

0.000589

Gnomad4 ASJ exome

AF:

0.00304

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00114

Gnomad4 FIN exome

AF:

0.000102

Gnomad4 NFE exome

AF:

0.00212

Gnomad4 OTH exome

AF:

0.00137

GnomAD4 genome

AF:

0.00117

AC:

179

AN:

152366

Hom.:

Cov.:

AF XY:

0.00103

AC XY:

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.000264

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00403

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.00213

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00132

Hom.:

Bravo

AF:

0.000997

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00234

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2023

MYC: BS1 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

DANN

Benign

0.74

FATHMM_MKL

Benign

0.18

MetaRNN

Benign

0.029

MutationTaster

Benign

1.0

GERP RS

1.8

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over