8-127735707-G-T

Variant names:

• chr8-127735707-G-T
• rs3824120
• ENST00000259523.10:c.-932G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001354870.1(MYC):​c.-887G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 398,952 control chromosomes in the GnomAD database, including 2,991 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 0.11 (1127 hom., cov: 32)
  • Exomes 𝑓: 0.12 (1864 hom.)
• Consequence: MYC NM_001354870.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.59
• Publications: 9 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0016974807).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001354870.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYC	NM_001354870.1		c.-887G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	NP_001341799.1	P01106-3
	MYC	NM_001354870.1		c.-887G>T		5_prime_UTR	Exon 1 of 3	NP_001341799.1	P01106-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYC	ENST00000259523.10	TSL:1	c.-932G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	ENSP00000259523.6	A0A0B4J1R1
	MYC	ENST00000517291.2	TSL:1	c.-283G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	ENSP00000429441.2	H0YBG3
	MYC	ENST00000259523.10	TSL:1	c.-932G>T		5_prime_UTR	Exon 1 of 3	ENSP00000259523.6	A0A0B4J1R1

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16687 AN: 152024 Hom.: 1127 Cov.: 32

Gnomad AFR AF: 0.0529

Gnomad AMI AF: 0.0800

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.0541

Gnomad EAS AF: 0.137

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.105

GnomAD4 exome AF: 0.118 AC: 29159 AN: 246810 Hom.: 1864 Cov.: 0 AF XY: 0.119 AC XY: 14903 AN XY: 125116

African (AFR) AF: 0.0504 AC: 362 AN: 7178

American (AMR) AF: 0.206 AC: 1533 AN: 7434

Ashkenazi Jewish (ASJ) AF: 0.0702 AC: 648 AN: 9234

East Asian (EAS) AF: 0.103 AC: 2369 AN: 22892

South Asian (SAS) AF: 0.146 AC: 442 AN: 3032

European-Finnish (FIN) AF: 0.127 AC: 2695 AN: 21278

Middle Eastern (MID) AF: 0.0563 AC: 73 AN: 1296

European-Non Finnish (NFE) AF: 0.121 AC: 19157 AN: 158078

Other (OTH) AF: 0.115 AC: 1880 AN: 16388

GnomAD4 genome AF: 0.110 AC: 16697 AN: 152142 Hom.: 1127 Cov.: 32 AF XY: 0.112 AC XY: 8316 AN XY: 74360

African (AFR) AF: 0.0529 AC: 2196 AN: 41526

American (AMR) AF: 0.194 AC: 2961 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0541 AC: 188 AN: 3472

East Asian (EAS) AF: 0.138 AC: 713 AN: 5172

South Asian (SAS) AF: 0.152 AC: 729 AN: 4796

European-Finnish (FIN) AF: 0.125 AC: 1320 AN: 10588

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.122 AC: 8275 AN: 67988

Other (OTH) AF: 0.102 AC: 215 AN: 2108

Alfa AF: 0.115 Hom.: 1078

Bravo AF: 0.111

TwinsUK AF: 0.106 AC: 392

ALSPAC AF: 0.122 AC: 472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.59
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.011
DANN	Benign	0.77
DEOGEN2	Benign	0.076	T
FATHMM_MKL	Benign	0.0048	N
LIST_S2	Benign	0.32	T
MetaRNN	Benign	0.0017	T
PhyloP100		-5.6
GERP RS		-7.5
PromoterAI		-0.017	Neutral
Mutation Taster		=299/1	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs3824120; hg19: chr8-128747953; COSMIC: COSV52373787; COSMIC: COSV52373787;