rs4645943

Variant names:

• chr8-127735225-C-T
• rs4645943
• ENST00000672942.1:n.195-1266G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000672942.1(CASC11):​n.195-1266G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 152,032 control chromosomes in the GnomAD database, including 2,596 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 0.14 (2596 hom., cov: 32)
• Consequence: CASC11 ENST00000672942.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.125

Genes affected

CASC11 (HGNC:48939): (cancer susceptibility 11)

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYC	NM_001354870.1	c.-1369C>T		upstream_gene_variant			NP_001341799.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASC11	ENST00000672942.1	n.195-1266G>A		intron_variant	Intron 1 of 2
MYC	ENST00000259523.10	c.-1414C>T		upstream_gene_variant		1		ENSP00000259523.6
MYC	ENST00000641252.1	c.-248C>T		upstream_gene_variant				ENSP00000493139.1

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21281 AN: 151912 Hom.: 2587 Cov.: 32

Gnomad AFR AF: 0.315

Gnomad AMI AF: 0.0220

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.0577

Gnomad EAS AF: 0.273

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.0930

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0431

Gnomad OTH AF: 0.0931

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.140 AC: 21329 AN: 152032 Hom.: 2596 Cov.: 32 AF XY: 0.144 AC XY: 10702 AN XY: 74322

Gnomad4 AFR AF: 0.315

Gnomad4 AMR AF: 0.112

Gnomad4 ASJ AF: 0.0577

Gnomad4 EAS AF: 0.274

Gnomad4 SAS AF: 0.167

Gnomad4 FIN AF: 0.0930

Gnomad4 NFE AF: 0.0431

Gnomad4 OTH AF: 0.0926

Alfa AF: 0.0705 Hom.: 548

Bravo AF: 0.144

Asia WGS AF: 0.206 AC: 717 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.8
DANN	Benign	0.69

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4645943; hg19: chr8-128747471; COSMIC: COSV104583428;