Genetic Variant MYC:c.802+61T>C (chr8-127739080-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_002467.6(MYC):c.802+61T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00576 in 1,411,290 control chromosomes in the GnomAD database, including 161 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 0.016 ( 44 hom., cov: 33)

Exomes 𝑓: 0.0045 ( 117 hom. )

Consequence

MYC
NM_002467.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.737

Publications

4 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 (BayesDel_noAF=-0.9).

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.016 (2436/152308) while in subpopulation EAS AF = 0.0446 (231/5178). AF 95% confidence interval is 0.0399. There are 44 homozygotes in GnomAd4. There are 1197 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 44 Unknown gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYC	NM_002467.6 link	c.802+61T>C		intron_variant	Intron 2 of 2	ENST00000621592.8	NP_002458.2
MYC	NM_001354870.1 link	c.799+61T>C		intron_variant	Intron 2 of 2		NP_001341799.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYC	ENST00000621592.8 link	c.802+61T>C		intron_variant	Intron 2 of 2	1	NM_002467.6	ENSP00000478887.2

Frequencies

GnomAD3 genomes

AF:

0.0160

AC:

2434

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0398

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00399

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0445

Gnomad SAS

AF:

0.0319

Gnomad FIN

AF:

0.0215

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00123

Gnomad OTH

AF:

0.0134

GnomAD4 exome

AF:

0.00452

AC:

5692

AN:

1258982

Hom.:

117

AF XY:

0.00506

AC XY:

3085

AN XY:

610060

show subpopulations

African (AFR)

AF:

0.0394

AC:

1093

AN:

27722

American (AMR)

AF:

0.00281

AC:

AN:

18132

Ashkenazi Jewish (ASJ)

AF:

0.0000539

AC:

AN:

18570

East Asian (EAS)

AF:

0.0322

AC:

1090

AN:

33848

South Asian (SAS)

AF:

0.0286

AC:

1740

AN:

60890

European-Finnish (FIN)

AF:

0.0197

AC:

600

AN:

30438

Middle Eastern (MID)

AF:

0.00289

AC:

AN:

4840

European-Non Finnish (NFE)

AF:

0.000601

AC:

608

AN:

1011934

Other (OTH)

AF:

0.00941

AC:

495

AN:

52608

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

289

579

868

1158

1447

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

192

288

384

480

<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:

0.0160

AC:

2436

AN:

152308

Hom.:

Cov.:

AF XY:

0.0161

AC XY:

1197

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.0397

AC:

1652

AN:

41562

American (AMR)

AF:

0.00398

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.0446

AC:

231

AN:

5178

South Asian (SAS)

AF:

0.0315

AC:

152

AN:

4830

European-Finnish (FIN)

AF:

0.0215

AC:

228

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00123

AC:

AN:

68022

Other (OTH)

AF:

0.0133

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

115

231

346

462

577

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

160

<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:

0.00965

Hom.:

Bravo

AF:

0.0149

Asia WGS

AF:

0.0310

AC:

109

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

2.1

(source)

DANN

Benign

0.43

PhyloP100

-0.74

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

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