dbSNP rs3891248: MYC:c.31-355T>A (chr8-127737893-T-A) – 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.31-355T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 152,062 control chromosomes in the GnomAD database, including 10,033 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 0.30 ( 10033 hom., cov: 33)

Consequence

MYC
NM_002467.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.132

Publications

20 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:

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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=-0.66).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.602 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002467.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYC	NM_002467.6	MANE Select	c.31-355T>A		intron	N/A	NP_002458.2	P01106-2
	MYC	NM_001354870.1		c.31-358T>A		intron	N/A	NP_001341799.1	P01106-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MYC	ENST00000621592.8	TSL:1 MANE Select	c.31-355T>A	intron	N/A	ENSP00000478887.2	P01106-2
MYC	ENST00000524013.2	TSL:1	c.31-358T>A	intron	N/A	ENSP00000430235.2	P01106-3
MYC	ENST00000377970.6	TSL:1	c.-15-355T>A	intron	N/A	ENSP00000367207.3	P01106-1

Frequencies

GnomAD3 genomes

AF:

0.303

AC:

46096

AN:

151944

Hom.:

10003

Cov.:

show subpopulations

Gnomad AFR

AF:

0.608

Gnomad AMI

AF:

0.107

Gnomad AMR

AF:

0.250

Gnomad ASJ

AF:

0.221

Gnomad EAS

AF:

0.405

Gnomad SAS

AF:

0.309

Gnomad FIN

AF:

0.204

Gnomad MID

AF:

0.234

Gnomad NFE

AF:

0.146

Gnomad OTH

AF:

0.264

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.304

AC:

46172

AN:

152062

Hom.:

10033

Cov.:

AF XY:

0.308

AC XY:

22896

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.609

AC:

25229

AN:

41460

American (AMR)

AF:

0.250

AC:

3817

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.221

AC:

768

AN:

3470

East Asian (EAS)

AF:

0.405

AC:

2080

AN:

5132

South Asian (SAS)

AF:

0.308

AC:

1480

AN:

4812

European-Finnish (FIN)

AF:

0.204

AC:

2157

AN:

10596

Middle Eastern (MID)

AF:

0.228

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.146

AC:

9919

AN:

67976

Other (OTH)

AF:

0.264

AC:

557

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1370

2740

4111

5481

6851

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

436

872

1308

1744

2180

<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:

0.233

Hom.:

820

Bravo

AF:

0.316

Asia WGS

AF:

0.343

AC:

1194

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

7.2

(source)

DANN

Benign

0.87

PhyloP100

-0.13

PromoterAI

-0.11

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over