Genetic Variant MYC:c.-96C>T (chr8-127736498-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_002467.6(MYC):c.-96C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00916 in 1,413,208 control chromosomes in the GnomAD database, including 105 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0089 ( 12 hom., cov: 32)

Exomes 𝑓: 0.0092 ( 93 hom. )

Consequence

MYC
NM_002467.6 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.08

Publications

6 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 -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 8-127736498-C-T is Benign according to our data. Variant chr8-127736498-C-T is described in ClinVar as Benign. ClinVar VariationId is 2658811.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 12 Unknown gene

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.-96C>T		5_prime_UTR	Exon 1 of 3	NP_002458.2	P01106-2
	MYC	NM_001354870.1		c.-96C>T		5_prime_UTR	Exon 1 of 3	NP_001341799.1	P01106-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MYC	ENST00000621592.8	TSL:1 MANE Select	c.-96C>T	5_prime_UTR	Exon 1 of 3	ENSP00000478887.2	P01106-2
MYC	ENST00000524013.2	TSL:1	c.-96C>T	5_prime_UTR	Exon 1 of 3	ENSP00000430235.2	P01106-3
MYC	ENST00000377970.6	TSL:1	c.-141C>T	5_prime_UTR	Exon 1 of 3	ENSP00000367207.3	P01106-1

Frequencies

GnomAD3 genomes

AF:

0.00888

AC:

1351

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00137

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00759

Gnomad ASJ

AF:

0.0173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0350

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0108

Gnomad OTH

AF:

0.00431

GnomAD4 exome

AF:

0.00920

AC:

11595

AN:

1260882

Hom.:

Cov.:

AF XY:

0.00905

AC XY:

5749

AN XY:

635206

show subpopulations

African (AFR)

AF:

0.00115

AC:

AN:

28576

American (AMR)

AF:

0.00401

AC:

159

AN:

39622

Ashkenazi Jewish (ASJ)

AF:

0.0177

AC:

426

AN:

24064

East Asian (EAS)

AF:

0.00

AC:

AN:

38580

South Asian (SAS)

AF:

0.000152

AC:

AN:

79064

European-Finnish (FIN)

AF:

0.0338

AC:

1702

AN:

50386

Middle Eastern (MID)

AF:

0.00328

AC:

AN:

3968

European-Non Finnish (NFE)

AF:

0.00920

AC:

8681

AN:

943116

Other (OTH)

AF:

0.0106

AC:

569

AN:

53506

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

599

1198

1798

2397

2996

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

270

540

810

1080

1350

<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:

0.00887

AC:

1351

AN:

152326

Hom.:

Cov.:

AF XY:

0.00920

AC XY:

685

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.00137

AC:

AN:

41584

American (AMR)

AF:

0.00758

AC:

116

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0173

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0350

AC:

372

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0108

AC:

737

AN:

68024

Other (OTH)

AF:

0.00427

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

133

200

266

333

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00805

Hom.:

Bravo

AF:

0.00687

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Benign

0.91

PhyloP100

1.1

PromoterAI

0.014

Neutral

(source)

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.1

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over