rs4645962

Positions:

• chr8-127739080-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.737

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=-0.9).
• 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 male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2436 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYC	NM_002467.6	c.802+61T>C		intron_variant		ENST00000621592.8	NP_002458.2
MYC	NM_001354870.1	c.799+61T>C		intron_variant			NP_001341799.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYC	ENST00000621592.8	c.802+61T>C		intron_variant		1	NM_002467.6	ENSP00000478887.2

Frequencies

GnomAD3 genomes AF: 0.0160 AC: 2434 AN: 152190 Hom.: 44 Cov.: 33

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

Gnomad4 AFR exome AF: 0.0394

Gnomad4 AMR exome AF: 0.00281

Gnomad4 ASJ exome AF: 0.0000539

Gnomad4 EAS exome AF: 0.0322

Gnomad4 SAS exome AF: 0.0286

Gnomad4 FIN exome AF: 0.0197

Gnomad4 NFE exome AF: 0.000601

Gnomad4 OTH exome AF: 0.00941

GnomAD4 genome AF: 0.0160 AC: 2436 AN: 152308 Hom.: 44 Cov.: 33 AF XY: 0.0161 AC XY: 1197 AN XY: 74478

Gnomad4 AFR AF: 0.0397

Gnomad4 AMR AF: 0.00398

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0446

Gnomad4 SAS AF: 0.0315

Gnomad4 FIN AF: 0.0215

Gnomad4 NFE AF: 0.00123

Gnomad4 OTH AF: 0.0133

Alfa AF: 0.00860 Hom.: 4

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
DANN	Benign	0.43
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs4645962; hg19: chr8-128751326;