8-127735822-G-A

Variant names:

• chr8-127735822-G-A
• rs117576103
• ENST00000259523:c.-817G>A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001354870.1(MYC):​c.-772G>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 0.00545 in 399,132 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0049 (8 hom., cov: 32)
  • Exomes 𝑓: 0.0058 (5 hom.)
• Consequence: MYC NM_001354870.1 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.502

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 8-127735822-G-A is Benign according to our data. Variant chr8-127735822-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3770573.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 742 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYC	NM_001354870.1	c.-772G>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	ENST00000259523	c.-817G>A		5_prime_UTR_variant	Exon 1 of 3	1		ENSP00000259523.6
MYC	ENST00000517291	c.-168G>A		5_prime_UTR_variant	Exon 1 of 3	1		ENSP00000429441.2
MYC	ENST00000651626	c.-298G>A		5_prime_UTR_variant	Exon 1 of 3			ENSP00000499182.1

Frequencies

GnomAD3 genomes AF: 0.00488 AC: 743 AN: 152152 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.00130

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000851

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00443

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00902

Gnomad OTH AF: 0.00239

GnomAD4 exome AF: 0.00581 AC: 1435 AN: 246862 Hom.: 5 Cov.: 0 AF XY: 0.00562 AC XY: 703 AN XY: 125170

Gnomad4 AFR exome AF: 0.00125

Gnomad4 AMR exome AF: 0.000672

Gnomad4 ASJ exome AF: 0.000433

Gnomad4 EAS exome AF: 0.0000437

Gnomad4 SAS exome AF: 0.000337

Gnomad4 FIN exome AF: 0.00678

Gnomad4 NFE exome AF: 0.00756

Gnomad4 OTH exome AF: 0.00458

GnomAD4 genome AF: 0.00487 AC: 742 AN: 152270 Hom.: 8 Cov.: 32 AF XY: 0.00446 AC XY: 332 AN XY: 74444

Gnomad4 AFR AF: 0.00130

Gnomad4 AMR AF: 0.000850

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00443

Gnomad4 NFE AF: 0.00901

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00414 Hom.: 0

Bravo AF: 0.00455

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jan 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

MYC: BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	9.9
DANN	Benign	0.87

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs117576103; hg19: chr8-128748068;