rs3891248

Positions:

• chr8-127737893-T-A
• chr8-127737893-T-C

Variant summary

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

The NM_002467.6(MYC):​c.31-355T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 152,062 control chromosomes in the GnomAD database, including 10,033 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 0.30 (10033 hom., cov: 33)
• Consequence: MYC NM_002467.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.132

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.602 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYC	NM_002467.6	c.31-355T>A		intron_variant		ENST00000621592.8	NP_002458.2
MYC	NM_001354870.1	c.31-358T>A		intron_variant			NP_001341799.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYC	ENST00000621592.8	c.31-355T>A		intron_variant		1	NM_002467.6	ENSP00000478887	A2

Frequencies

GnomAD3 genomes AF: 0.303 AC: 46096 AN: 151944 Hom.: 10003 Cov.: 33

Gnomad AFR AF: 0.608

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.405

Gnomad SAS AF: 0.309

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.264

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

GnomAD4 genome AF: 0.304 AC: 46172 AN: 152062 Hom.: 10033 Cov.: 33 AF XY: 0.308 AC XY: 22896 AN XY: 74350

Gnomad4 AFR AF: 0.609

Gnomad4 AMR AF: 0.250

Gnomad4 ASJ AF: 0.221

Gnomad4 EAS AF: 0.405

Gnomad4 SAS AF: 0.308

Gnomad4 FIN AF: 0.204

Gnomad4 NFE AF: 0.146

Gnomad4 OTH AF: 0.264

Alfa AF: 0.233 Hom.: 820

Bravo AF: 0.316

Asia WGS AF: 0.343 AC: 1194 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	7.2
DANN	Benign	0.87

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs3891248; hg19: chr8-128750139; COSMIC: COSV52379704; COSMIC: COSV52379704;