8-127742443-C-T

Position:

• chr8-127742443-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002467.6(MYC):​c.*1485C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0256 in 152,264 control chromosomes in the GnomAD database, including 104 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 0.026 (104 hom., cov: 32)
• Consequence: MYC NM_002467.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.708

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYC	NM_002467.6	c.*1485C>T		3_prime_UTR_variant	3/3	ENST00000621592.8	NP_002458.2
MYC	NM_001354870.1	c.*1485C>T		3_prime_UTR_variant	3/3		NP_001341799.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYC	ENST00000621592.8	c.*1485C>T		3_prime_UTR_variant	3/3	1	NM_002467.6	ENSP00000478887.2

Frequencies

GnomAD3 genomes AF: 0.0255 AC: 3882 AN: 152146 Hom.: 105 Cov.: 32

Gnomad AFR AF: 0.0219

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0267

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.108

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.00508

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0198

Gnomad OTH AF: 0.0177

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

GnomAD4 genome AF: 0.0256 AC: 3892 AN: 152264 Hom.: 104 Cov.: 32 AF XY: 0.0275 AC XY: 2051 AN XY: 74468

Gnomad4 AFR AF: 0.0220

Gnomad4 AMR AF: 0.0269

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.108

Gnomad4 SAS AF: 0.117

Gnomad4 FIN AF: 0.00508

Gnomad4 NFE AF: 0.0198

Gnomad4 OTH AF: 0.0175

Alfa AF: 0.0157 Hom.: 7

Bravo AF: 0.0244

Asia WGS AF: 0.0950 AC: 330 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.1
DANN	Benign	0.79

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4645974; hg19: chr8-128754689;