dbSNP rs4645943: CASC11:n.72G>A (chr8-127735225-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000774805.1(CASC11):n.72G>A variant causes a non coding transcript exon 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
ENST00000774805.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.125

Publications

23 publications found

Variant links:

COSMIC-nc: COSV104583428

Genes affected

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

CASC11 links:

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]

MYC Gene-Disease associations (from GenCC):

Burkitt lymphoma
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

MYC links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000774805.1. 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.-1369C>T		upstream_gene	N/A	NP_001341799.1	P01106-3

Ensembl Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank
CASC11	ENST00000774805.1	n.72G>A	non_coding_transcript_exon	Exon 1 of 3
CASC11	ENST00000774811.1	n.35G>A	non_coding_transcript_exon	Exon 1 of 2
CASC11	ENST00000672942.2	n.230-1266G>A	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.140

AC:

21281

AN:

151912

Hom.:

2587

Cov.:

show subpopulations

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.:

AF XY:

0.144

AC XY:

10702

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.315

AC:

13047

AN:

41394

American (AMR)

AF:

0.112

AC:

1718

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0577

AC:

200

AN:

3468

East Asian (EAS)

AF:

0.274

AC:

1405

AN:

5134

South Asian (SAS)

AF:

0.167

AC:

807

AN:

4822

European-Finnish (FIN)

AF:

0.0930

AC:

986

AN:

10604

Middle Eastern (MID)

AF:

0.0748

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0431

AC:

2929

AN:

68004

Other (OTH)

AF:

0.0926

AC:

195

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

802

1604

2406

3208

4010

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

216

432

648

864

1080

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0760

Hom.:

1057

Bravo

AF:

0.144

Asia WGS

AF:

0.206

AC:

717

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

4.8

(source)

DANN

Benign

0.69

PhyloP100

-0.13

PromoterAI

-0.064

Neutral

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over