rs3891248

Variant names:

• chr8-127737893-T-A
• rs3891248
• NM_002467.6:c.31-355T>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 20 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 (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 rank	MANE	Protein	UniProt
MYC	NM_002467.6	c.31-355T>A		intron_variant	Intron 1 of 2	ENST00000621592.8	NP_002458.2
MYC	NM_001354870.1	c.31-358T>A		intron_variant	Intron 1 of 2		NP_001341799.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYC	ENST00000621592.8	c.31-355T>A		intron_variant	Intron 1 of 2	1	NM_002467.6	ENSP00000478887.2

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

African (AFR) AF: 0.609 AC: 25229 AN: 41460

American (AMR) AF: 0.250 AC: 3817 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.221 AC: 768 AN: 3470

East Asian (EAS) AF: 0.405 AC: 2080 AN: 5132

South Asian (SAS) AF: 0.308 AC: 1480 AN: 4812

European-Finnish (FIN) AF: 0.204 AC: 2157 AN: 10596

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.146 AC: 9919 AN: 67976

Other (OTH) AF: 0.264 AC: 557 AN: 2112

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
PhyloP100		-0.13
PromoterAI		-0.11	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3891248; hg19: chr8-128750139; COSMIC: COSV52379704; COSMIC: COSV52379704;