8-127736498-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_002467.6(MYC):c.-96C>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 0.00916 in 1,413,208 control chromosomes in the GnomAD database, including 105 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0089 (12 hom., cov: 32)
  • Exomes 𝑓: 0.0092 (93 hom.)
• Consequence: MYC NM_002467.6 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.08

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 8-127736498-C-T is Benign according to our data. Variant chr8-127736498-C-T is described in ClinVar as [Benign]. Clinvar id is 2658811.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 1351 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYC	NM_002467.6	c.-96C>T		5_prime_UTR_variant	1/3	ENST00000621592.8
MYC	NM_001354870.1	c.-96C>T		5_prime_UTR_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYC	ENST00000621592.8	c.-96C>T		5_prime_UTR_variant	1/3	1	NM_002467.6	A2

Frequencies

GnomAD3 genomes AF: 0.00888 AC: 1351 AN: 152210 Hom.: 12 Cov.: 32

Gnomad AFR AF: 0.00137

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00759

Gnomad ASJ AF: 0.0173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0350

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0108

Gnomad OTH AF: 0.00431

GnomAD4 exome AF: 0.00920 AC: 11595 AN: 1260882 Hom.: 93 Cov.: 17 AF XY: 0.00905 AC XY: 5749 AN XY: 635206

Gnomad4 AFR exome AF: 0.00115

Gnomad4 AMR exome AF: 0.00401

Gnomad4 ASJ exome AF: 0.0177

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000152

Gnomad4 FIN exome AF: 0.0338

Gnomad4 NFE exome AF: 0.00920

Gnomad4 OTH exome AF: 0.0106

GnomAD4 genome AF: 0.00887 AC: 1351 AN: 152326 Hom.: 12 Cov.: 32 AF XY: 0.00920 AC XY: 685 AN XY: 74488

Gnomad4 AFR AF: 0.00137

Gnomad4 AMR AF: 0.00758

Gnomad4 ASJ AF: 0.0173

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0350

Gnomad4 NFE AF: 0.0108

Gnomad4 OTH AF: 0.00427

Alfa AF: 0.00805 Hom.: 1

Bravo AF: 0.00687

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

MYC: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
Cadd	Benign	16
Dann	Benign	0.91
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.1

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: rs4645949; hg19: chr8-128748744;