rs13250910

Positions:

• chr8-127735936-A-C
• chr8-127735936-A-G
• chr8-127735936-A-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000259523.10(MYC):​c.-703A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. 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 0.14 (0 hom., cov: 0)
  • Exomes 𝑓: 0.014 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MYC ENST00000259523.10 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0860

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 Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYC	NM_001354870.1	c.-658A>C		5_prime_UTR_variant	1/3		NP_001341799.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYC	ENST00000259523.10	c.-703A>C		5_prime_UTR_variant	1/3	1		ENSP00000259523
MYC	ENST00000517291.2	c.-154+100A>C		intron_variant		1		ENSP00000429441
MYC	ENST00000651626.1	c.-284+100A>C		intron_variant				ENSP00000499182
CASC11	ENST00000672942.1	n.195-1977T>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.00 AC: 6464 AN: 45188 Hom.: 0 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.0584

Gnomad SAS AF: 0.0971

Gnomad FIN AF: 0.0981

Gnomad MID AF: 0.0652

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.161

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0144 AC: 725 AN: 50436 Hom.: 0 Cov.: 0 AF XY: 0.0137 AC XY: 353 AN XY: 25684

Gnomad4 AFR exome AF: 0.0161

Gnomad4 AMR exome AF: 0.0164

Gnomad4 ASJ exome AF: 0.0149

Gnomad4 EAS exome AF: 0.0177

Gnomad4 SAS exome AF: 0.0134

Gnomad4 FIN exome AF: 0.00759

Gnomad4 NFE exome AF: 0.0147

Gnomad4 OTH exome AF: 0.0136

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.143 AC: 6462 AN: 45210 Hom.: 0 Cov.: 0 AF XY: 0.131 AC XY: 2900 AN XY: 22178

Gnomad4 AFR AF: 0.149

Gnomad4 AMR AF: 0.116

Gnomad4 ASJ AF: 0.153

Gnomad4 EAS AF: 0.0583

Gnomad4 SAS AF: 0.0971

Gnomad4 FIN AF: 0.0981

Gnomad4 NFE AF: 0.160

Gnomad4 OTH AF: 0.159

Alfa AF: 0.153 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.6
DANN	Benign	0.33

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs13250910; hg19: chr8-128748182;