dbSNP rs4645946: MYC:c.-500G>A (chr8-127736139-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The ENST00000377970.6(MYC):c.-500G>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 0.0194 in 432,244 control chromosomes in the GnomAD database, including 107 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 0.023 ( 54 hom., cov: 32)

Exomes 𝑓: 0.018 ( 53 hom. )

Consequence

MYC
ENST00000377970.6 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.249

Publications

10 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 links:

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

CASC11 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 (MetaRNN=0.004051447).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0228 (3467/152330) while in subpopulation AFR AF = 0.039 (1623/41564). AF 95% confidence interval is 0.0375. There are 54 homozygotes in GnomAd4. There are 1667 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 54 Unknown gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYC	NM_001354870.1 link	c.-455G>A		5_prime_UTR_variant	Exon 1 of 3		NP_001341799.1
MYC	NM_002467.6 link	c.-455G>A		upstream_gene_variant		ENST00000621592.8	NP_002458.2	P01106-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYC	ENST00000621592.8 link	c.-455G>A		upstream_gene_variant		1	NM_002467.6	ENSP00000478887.2		P01106-2

Frequencies

GnomAD3 genomes

AF:

0.0228

AC:

3468

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0392

Gnomad AMI

AF:

0.0296

Gnomad AMR

AF:

0.0137

Gnomad ASJ

AF:

0.0202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0207

Gnomad FIN

AF:

0.0146

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0180

Gnomad OTH

AF:

0.0244

GnomAD4 exome

AF:

0.0176

AC:

4914

AN:

279914

Hom.:

Cov.:

AF XY:

0.0176

AC XY:

2513

AN XY:

142512

show subpopulations

African (AFR)

AF:

0.0372

AC:

296

AN:

7954

American (AMR)

AF:

0.0128

AC:

136

AN:

10662

Ashkenazi Jewish (ASJ)

AF:

0.0178

AC:

175

AN:

9818

East Asian (EAS)

AF:

0.0000801

AC:

AN:

24966

South Asian (SAS)

AF:

0.0246

AC:

185

AN:

7520

European-Finnish (FIN)

AF:

0.0185

AC:

407

AN:

22002

Middle Eastern (MID)

AF:

0.0310

AC:

AN:

1388

European-Non Finnish (NFE)

AF:

0.0187

AC:

3326

AN:

177690

Other (OTH)

AF:

0.0192

AC:

344

AN:

17914

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

364

727

1091

1454

1818

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

<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:

0.0228

AC:

3467

AN:

152330

Hom.:

Cov.:

AF XY:

0.0224

AC XY:

1667

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.0390

AC:

1623

AN:

41564

American (AMR)

AF:

0.0137

AC:

210

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.0202

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.0209

AC:

101

AN:

4832

European-Finnish (FIN)

AF:

0.0146

AC:

155

AN:

10618

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0180

AC:

1225

AN:

68032

Other (OTH)

AF:

0.0241

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

174

348

523

697

871

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

176

220

<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:

0.0196

Hom.:

Bravo

AF:

0.0241

TwinsUK

AF:

0.0240

AC:

ALSPAC

AF:

0.0241

AC:

Asia WGS

AF:

0.0160

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.59

BayesDel_noAF

Benign

-0.59

CADD

Benign

6.3

(source)

DANN

Benign

0.97

FATHMM_MKL

Benign

0.043

MetaRNN

Benign

0.0041

PhyloP100

-0.25

GERP RS

-0.29

PromoterAI

0.037

Neutral

(source)

Mutation Taster

=300/0

polymorphism

(source)

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