Genetic Variant MYCBP2:c.3935+116A>G (chr13-77194037-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_015057.5(MYCBP2):c.3935+116A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0788 in 561,340 control chromosomes in the GnomAD database, including 2,229 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 0.096 ( 952 hom., cov: 32)

Exomes 𝑓: 0.072 ( 1277 hom. )

Consequence

MYCBP2
NM_015057.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.304

Publications

3 publications found

Variant links:

Genes affected

MYCBP2 (HGNC:23386): (MYC binding protein 2) This gene encodes an E3 ubiquitin-protein ligase and member of the PHR (Phr1/MYCBP2, highwire and RPM-1) family of proteins. The encoded protein plays a role in axon guidance and synapse formation in the developing nervous system. In mammalian cells, this protein regulates the cAMP and mTOR signaling pathways, and may additionally regulate autophagy. Reduced expression of this gene has been observed in acute lymphoblastic leukemia patients and a mutation in this gene has been identified in patients with a rare inherited vision defect. [provided by RefSeq, Mar 2017]

MYCBP2 links:

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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=-0.89).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015057.5. 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
	MYCBP2	NM_015057.5	MANE Select	c.3935+116A>G		intron	N/A	NP_055872.4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
MYCBP2	ENST00000544440.7	TSL:1 MANE Select	c.3935+116A>G	intron	N/A	ENSP00000444596.2
MYCBP2	ENST00000357337.11	TSL:1	c.3935+116A>G	intron	N/A	ENSP00000349892.6
MYCBP2	ENST00000683697.1		c.3935+116A>G	intron	N/A	ENSP00000508153.1

Frequencies

GnomAD3 genomes

AF:

0.0964

AC:

14656

AN:

152112

Hom.:

948

Cov.:

show subpopulations

Gnomad AFR

AF:

0.177

Gnomad AMI

AF:

0.0956

Gnomad AMR

AF:

0.0674

Gnomad ASJ

AF:

0.0928

Gnomad EAS

AF:

0.110

Gnomad SAS

AF:

0.0397

Gnomad FIN

AF:

0.0626

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.0621

Gnomad OTH

AF:

0.0883

GnomAD4 exome

AF:

0.0723

AC:

29571

AN:

409110

Hom.:

1277

AF XY:

0.0704

AC XY:

15104

AN XY:

214674

show subpopulations

African (AFR)

AF:

0.178

AC:

1952

AN:

10962

American (AMR)

AF:

0.0717

AC:

1021

AN:

14242

Ashkenazi Jewish (ASJ)

AF:

0.0829

AC:

1021

AN:

12310

East Asian (EAS)

AF:

0.121

AC:

3340

AN:

27710

South Asian (SAS)

AF:

0.0372

AC:

811

AN:

21830

European-Finnish (FIN)

AF:

0.0709

AC:

2689

AN:

37922

Middle Eastern (MID)

AF:

0.104

AC:

234

AN:

2254

European-Non Finnish (NFE)

AF:

0.0645

AC:

16750

AN:

259506

Other (OTH)

AF:

0.0783

AC:

1753

AN:

22374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1287

2574

3860

5147

6434

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

256

512

768

1024

1280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0965

AC:

14688

AN:

152230

Hom.:

952

Cov.:

AF XY:

0.0964

AC XY:

7172

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.177

AC:

7373

AN:

41538

American (AMR)

AF:

0.0674

AC:

1031

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0928

AC:

322

AN:

3468

East Asian (EAS)

AF:

0.111

AC:

574

AN:

5188

South Asian (SAS)

AF:

0.0399

AC:

193

AN:

4832

European-Finnish (FIN)

AF:

0.0626

AC:

664

AN:

10600

Middle Eastern (MID)

AF:

0.122

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0621

AC:

4224

AN:

67988

Other (OTH)

AF:

0.0870

AC:

184

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

668

1336

2004

2672

3340

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

154

308

462

616

770

<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:

0.0731

Hom.:

203

Bravo

AF:

0.103

Asia WGS

AF:

0.0780

AC:

272

AN:

3456

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

2.9

(source)

DANN

Benign

0.77

PhyloP100

-0.30

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over