dbSNP rs2070583: MYC:c.*50A>G (chr8-127741008-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002467.6(MYC):c.*50A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0291 in 1,473,676 control chromosomes in the GnomAD database, including 1,226 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 0.031 ( 165 hom., cov: 32)

Exomes 𝑓: 0.029 ( 1061 hom. )

Consequence

MYC
NM_002467.6 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.681

Publications

22 publications found

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 Gene-Disease associations (from GenCC):

Burkitt lymphoma
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

MYC links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYC	NM_002467.6 link	c.*50A>G		3_prime_UTR_variant	Exon 3 of 3	ENST00000621592.8	NP_002458.2	P01106-2
MYC	NM_001354870.1 link	c.*50A>G		3_prime_UTR_variant	Exon 3 of 3		NP_001341799.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYC	ENST00000621592.8 link	c.*50A>G		3_prime_UTR_variant	Exon 3 of 3	1	NM_002467.6	ENSP00000478887.2		P01106-2

Frequencies

GnomAD3 genomes

AF:

0.0313

AC:

4761

AN:

152150

Hom.:

163

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0199

Gnomad AMI

AF:

0.0164

Gnomad AMR

AF:

0.0707

Gnomad ASJ

AF:

0.0251

Gnomad EAS

AF:

0.148

Gnomad SAS

AF:

0.0869

Gnomad FIN

AF:

0.00895

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0209

Gnomad OTH

AF:

0.0224

GnomAD2 exomes

AF:

0.0416

AC:

6559

AN:

157744

AF XY:

0.0422

show subpopulations

Gnomad AFR exome

AF:

0.0200

Gnomad AMR exome

AF:

0.0450

Gnomad ASJ exome

AF:

0.0212

Gnomad EAS exome

AF:

0.151

Gnomad FIN exome

AF:

0.0129

Gnomad NFE exome

AF:

0.0194

Gnomad OTH exome

AF:

0.0312

GnomAD4 exome

AF:

0.0289

AC:

38141

AN:

1321406

Hom.:

1061

Cov.:

AF XY:

0.0303

AC XY:

19620

AN XY:

646850

show subpopulations

African (AFR)

AF:

0.0189

AC:

560

AN:

29664

American (AMR)

AF:

0.0442

AC:

1210

AN:

27370

Ashkenazi Jewish (ASJ)

AF:

0.0198

AC:

386

AN:

19542

East Asian (EAS)

AF:

0.144

AC:

5552

AN:

38662

South Asian (SAS)

AF:

0.0893

AC:

5813

AN:

65120

European-Finnish (FIN)

AF:

0.0121

AC:

484

AN:

40032

Middle Eastern (MID)

AF:

0.00917

AC:

AN:

5234

European-Non Finnish (NFE)

AF:

0.0215

AC:

22415

AN:

1040940

Other (OTH)

AF:

0.0305

AC:

1673

AN:

54842

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1808

3617

5425

7234

9042

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1022

2044

3066

4088

5110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0313

AC:

4765

AN:

152270

Hom.:

165

Cov.:

AF XY:

0.0344

AC XY:

2563

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.0198

AC:

824

AN:

41542

American (AMR)

AF:

0.0710

AC:

1087

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0251

AC:

AN:

3472

East Asian (EAS)

AF:

0.148

AC:

766

AN:

5168

South Asian (SAS)

AF:

0.0869

AC:

419

AN:

4820

European-Finnish (FIN)

AF:

0.00895

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0209

AC:

1424

AN:

68030

Other (OTH)

AF:

0.0217

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

226

452

678

904

1130

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

180

240

300

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0236

Hom.:

Bravo

AF:

0.0318

Asia WGS

AF:

0.0960

AC:

335

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.6

(source)

DANN

Benign

0.58

PhyloP100

0.68

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over