rs4645948

Positions:

• chr8-127736252-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4 BA1

The NM_002467.6(MYC):​c.-342C>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 0.0319 in 531,178 control chromosomes in the GnomAD database, including 639 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 0.030 (148 hom., cov: 32)
  • Exomes 𝑓: 0.033 (491 hom.)
• Consequence: MYC NM_002467.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.92

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]

CASC11 (HGNC:48939): (cancer susceptibility 11)

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.1).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYC	NM_002467.6	c.-342C>T		5_prime_UTR_variant	1/3	ENST00000621592.8	NP_002458.2
MYC	NM_001354870.1	c.-342C>T		5_prime_UTR_variant	1/3		NP_001341799.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYC	ENST00000621592.8	c.-342C>T		5_prime_UTR_variant	1/3	1	NM_002467.6	ENSP00000478887	A2

Frequencies

GnomAD3 genomes AF: 0.0300 AC: 4560 AN: 152170 Hom.: 149 Cov.: 32

Gnomad AFR AF: 0.0191

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.0668

Gnomad ASJ AF: 0.0141

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.0879

Gnomad FIN AF: 0.00885

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0203

Gnomad OTH AF: 0.0211

GnomAD4 exome AF: 0.0327 AC: 12396 AN: 378890 Hom.: 491 Cov.: 0 AF XY: 0.0346 AC XY: 6819 AN XY: 196966

Gnomad4 AFR exome AF: 0.0196

Gnomad4 AMR exome AF: 0.0387

Gnomad4 ASJ exome AF: 0.0125

Gnomad4 EAS exome AF: 0.136

Gnomad4 SAS exome AF: 0.0819

Gnomad4 FIN exome AF: 0.0116

Gnomad4 NFE exome AF: 0.0192

Gnomad4 OTH exome AF: 0.0245

GnomAD4 genome AF: 0.0300 AC: 4563 AN: 152288 Hom.: 148 Cov.: 32 AF XY: 0.0331 AC XY: 2468 AN XY: 74454

Gnomad4 AFR AF: 0.0190

Gnomad4 AMR AF: 0.0670

Gnomad4 ASJ AF: 0.0141

Gnomad4 EAS AF: 0.143

Gnomad4 SAS AF: 0.0878

Gnomad4 FIN AF: 0.00885

Gnomad4 NFE AF: 0.0203

Gnomad4 OTH AF: 0.0208

Alfa AF: 0.0197 Hom.: 83

Bravo AF: 0.0304

Asia WGS AF: 0.0920 AC: 319 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.10
CADD	Benign	22
DANN	Uncertain	0.98
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.3

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

LitVar

Other links and lift over

dbSNP: rs4645948; hg19: chr8-128748498; COSMIC: COSV52368217; COSMIC: COSV52368217;