ENST00000259523.10:c.-817G>A

Variant names:

• chr8-127735822-G-A
• rs117576103
• ENST00000259523.10:c.-817G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The ENST00000259523.10(MYC):​c.-817G>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 ENST00000259523.10 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.502
• Publications: 1 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 -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 VariationId is 3770573.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 8 Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000259523.10. 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.-772G>A		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.-817G>A		5_prime_UTR	Exon 1 of 3	ENSP00000259523.6	A0A0B4J1R1
	MYC	ENST00000517291.2	TSL:1	c.-168G>A		5_prime_UTR	Exon 1 of 3	ENSP00000429441.2	H0YBG3
	MYC	ENST00000651626.1		c.-298G>A		5_prime_UTR	Exon 1 of 3	ENSP00000499182.1	A0A494C1T8

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

African (AFR) AF: 0.00125 AC: 9 AN: 7180

American (AMR) AF: 0.000672 AC: 5 AN: 7436

Ashkenazi Jewish (ASJ) AF: 0.000433 AC: 4 AN: 9240

East Asian (EAS) AF: 0.0000437 AC: 1 AN: 22896

South Asian (SAS) AF: 0.000337 AC: 1 AN: 2964

European-Finnish (FIN) AF: 0.00678 AC: 144 AN: 21244

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1294

European-Non Finnish (NFE) AF: 0.00756 AC: 1196 AN: 158222

Other (OTH) AF: 0.00458 AC: 75 AN: 16386

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

African (AFR) AF: 0.00130 AC: 54 AN: 41550

American (AMR) AF: 0.000850 AC: 13 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4820

European-Finnish (FIN) AF: 0.00443 AC: 47 AN: 10618

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00901 AC: 613 AN: 68026

Other (OTH) AF: 0.00237 AC: 5 AN: 2110

Alfa AF: 0.00575 Hom.: 0

Bravo AF: 0.00455

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	9.9
DANN	Benign	0.87
PhyloP100		0.50
PromoterAI		0.047	Neutral
Mutation Taster		=291/9	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs117576103; hg19: chr8-128748068;