rs4645948

Variant names:

• chr8-127736252-C-A
• rs4645948
• NM_002467.6:c.-342C>A

Your query was ambiguous. Multiple possible variants found:

• chr8-127736252-C-A
• chr8-127736252-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002467.6(MYC):​c.-342C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000264 in 378,948 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000026 (0 hom.)
• Consequence: MYC NM_002467.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.92
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2891472).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYC	NM_002467.6	c.-342C>A		5_prime_UTR_variant	Exon 1 of 3	ENST00000621592.8	NP_002458.2
MYC	NM_001354870.1	c.-342C>A		5_prime_UTR_variant	Exon 1 of 3		NP_001341799.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYC	ENST00000621592.8	c.-342C>A		5_prime_UTR_variant	Exon 1 of 3	1	NM_002467.6	ENSP00000478887.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000264 AC: 1 AN: 378948 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 196996

African (AFR) AF: 0.00 AC: 0 AN: 10836

American (AMR) AF: 0.00 AC: 0 AN: 12756

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12196

East Asian (EAS) AF: 0.00 AC: 0 AN: 28010

South Asian (SAS) AF: 0.00 AC: 0 AN: 28418

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27170

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1748

European-Non Finnish (NFE) AF: 0.00000425 AC: 1 AN: 235044

Other (OTH) AF: 0.00 AC: 0 AN: 22770

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.90
BayesDel_noAF	Benign	-0.10
CADD	Benign	22
DANN	Benign	0.97
FATHMM_MKL	Benign	0.51	D
MetaRNN	Benign	0.29	T
PhyloP100		1.9
GERP RS		2.6
PromoterAI		-0.066	Neutral
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.3
Mutation Taster		=300/0	polymorphism

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

Other links and lift over

dbSNP: rs4645948; hg19: chr8-128748498;