chr8-127738281-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 1P and 16B. PP2BP4_StrongBP6_Very_StrongBS2

The NM_002467.6(MYC):c.64T>C(p.Phe22Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00196 in 1,604,432 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0023 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0019 ( 23 hom. )

Consequence

MYC
NM_002467.6 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.635

Publications

24 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 -15 ACMG points.

PP2

Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 11 curated pathogenic missense variants (we use a threshold of 10). The gene has 2 curated benign missense variants. Gene score misZ: 1.2227 (below the threshold of 3.09). Trascript score misZ: 1.518 (below the threshold of 3.09). GenCC associations: The gene is linked to Burkitt lymphoma.

BP4

Computational evidence support a benign effect (MetaRNN=0.0024340153).

BP6

Variant 8-127738281-T-C is Benign according to our data. Variant chr8-127738281-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 722844.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 2 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.64T>C	p.Phe22Leu	missense	Exon 2 of 3	NP_002458.2	P01106-2
	MYC	NM_001354870.1		c.61T>C	p.Phe21Leu	missense	Exon 2 of 3	NP_001341799.1	P01106-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MYC	ENST00000621592.8	TSL:1 MANE Select	c.64T>C	p.Phe22Leu	missense	Exon 2 of 3	ENSP00000478887.2	P01106-2
MYC	ENST00000524013.2	TSL:1	c.61T>C	p.Phe21Leu	missense	Exon 2 of 3	ENSP00000430235.2	P01106-3
MYC	ENST00000377970.6	TSL:1	c.19T>C	p.Phe7Leu	missense	Exon 2 of 3	ENSP00000367207.3	P01106-1

Frequencies

GnomAD3 genomes

AF:

0.00225

AC:

343

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.00425

Gnomad ASJ

AF:

0.0458

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00135

Gnomad OTH

AF:

0.00334

GnomAD2 exomes

AF:

0.00278

AC:

689

AN:

247448

AF XY:

0.00268

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.00212

Gnomad ASJ exome

AF:

0.0366

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000186

Gnomad NFE exome

AF:

0.00147

Gnomad OTH exome

AF:

0.00631

GnomAD4 exome

AF:

0.00193

AC:

2797

AN:

1452110

Hom.:

Cov.:

AF XY:

0.00193

AC XY:

1393

AN XY:

720620

show subpopulations

African (AFR)

AF:

0.000180

AC:

AN:

33276

American (AMR)

AF:

0.00198

AC:

AN:

44042

Ashkenazi Jewish (ASJ)

AF:

0.0391

AC:

1011

AN:

25854

East Asian (EAS)

AF:

0.00

AC:

AN:

39474

South Asian (SAS)

AF:

0.00169

AC:

145

AN:

85586

European-Finnish (FIN)

AF:

0.000188

AC:

AN:

53258

Middle Eastern (MID)

AF:

0.00732

AC:

AN:

5736

European-Non Finnish (NFE)

AF:

0.00110

AC:

1218

AN:

1104980

Other (OTH)

AF:

0.00464

AC:

278

AN:

59904

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

159

318

476

635

794

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

132

198

264

330

<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:

0.00225

AC:

343

AN:

152322

Hom.:

Cov.:

AF XY:

0.00224

AC XY:

167

AN XY:

74492

show subpopulations

African (AFR)

AF:

0.000168

AC:

AN:

41560

American (AMR)

AF:

0.00425

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0458

AC:

159

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00124

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0000941

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00135

AC:

AN:

68028

Other (OTH)

AF:

0.00331

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00271

Hom.:

Bravo

AF:

0.00205

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00337

AC:

ExAC

AF:

0.00227

AC:

276

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00300

EpiControl

AF:

0.00249

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.53

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.67

CADD

Benign

(source)

DANN

Benign

0.83

DEOGEN2

Benign

0.21

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.38

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.73

M_CAP

Benign

0.0034

MetaRNN

Benign

0.0024

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.20

PhyloP100

0.64

PrimateAI

Benign

0.47

PROVEAN

Benign

1.1

REVEL

Benign

0.061

Sift

Benign

0.76

Sift4G

Benign

1.0

Polyphen

0.0010

Vest4

0.11

MutPred

0.47

Gain of glycosylation at S6 (P = 0.091)

MVP

0.22

ClinPred

0.00043

GERP RS

3.9

Varity_R

0.10

gMVP

0.15

Mutation Taster

=97/3

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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