rs13250910

Variant names:

• chr8-127735936-A-C
• rs13250910
• ENST00000259523.10:c.-703A>C

Your query was ambiguous. Multiple possible variants found:

• chr8-127735936-A-C
• chr8-127735936-A-G
• chr8-127735936-A-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000259523.10(MYC):​c.-703A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. 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 (0 hom., cov: 0)
  • Exomes 𝑓: 0.014 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MYC ENST00000259523.10 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0860
• Publications: 3 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYC	NM_001354870.1	c.-658A>C		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	ENST00000259523.10	c.-703A>C		5_prime_UTR_variant	Exon 1 of 3	1		ENSP00000259523.6
MYC	ENST00000517291.2	c.-154+100A>C		intron_variant	Intron 1 of 2	1		ENSP00000429441.2
CASC11	ENST00000774799.1	n.209T>G		non_coding_transcript_exon_variant	Exon 1 of 3

Frequencies

GnomAD3 genomes AF: 0.143 AC: 6464 AN: 45188 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.0584

Gnomad SAS AF: 0.0971

Gnomad FIN AF: 0.0981

Gnomad MID AF: 0.0652

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.161

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0144 AC: 725 AN: 50436 Hom.: 0 Cov.: 0 AF XY: 0.0137 AC XY: 353 AN XY: 25684

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0161 AC: 22 AN: 1370

American (AMR) AF: 0.0164 AC: 27 AN: 1642

Ashkenazi Jewish (ASJ) AF: 0.0149 AC: 27 AN: 1818

East Asian (EAS) AF: 0.0177 AC: 78 AN: 4414

South Asian (SAS) AF: 0.0134 AC: 6 AN: 448

European-Finnish (FIN) AF: 0.00759 AC: 29 AN: 3820

Middle Eastern (MID) AF: 0.00352 AC: 1 AN: 284

European-Non Finnish (NFE) AF: 0.0147 AC: 490 AN: 33326

Other (OTH) AF: 0.0136 AC: 45 AN: 3314

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.143 AC: 6462 AN: 45210 Hom.: 0 Cov.: 0 AF XY: 0.131 AC XY: 2900 AN XY: 22178

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.149 AC: 1739 AN: 11656

American (AMR) AF: 0.116 AC: 454 AN: 3902

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 164 AN: 1074

East Asian (EAS) AF: 0.0583 AC: 110 AN: 1886

South Asian (SAS) AF: 0.0971 AC: 149 AN: 1534

European-Finnish (FIN) AF: 0.0981 AC: 282 AN: 2874

Middle Eastern (MID) AF: 0.0698 AC: 6 AN: 86

European-Non Finnish (NFE) AF: 0.160 AC: 3399 AN: 21250

Other (OTH) AF: 0.159 AC: 98 AN: 618

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.153 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.6
DANN	Benign	0.33
PhyloP100		0.086
PromoterAI		-0.012	Neutral
Mutation Taster		=299/1	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs13250910; hg19: chr8-128748182;