chr13-77194037-T-C

Variant names:

• chr13-77194037-T-C
• rs1041242
• NM_015057.5:c.3935+116A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.304
• Publications: 3 publications found

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]

ACMG classification

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYCBP2	NM_015057.5	c.3935+116A>G		intron_variant	Intron 27 of 82	ENST00000544440.7	NP_055872.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYCBP2	ENST00000544440.7	c.3935+116A>G		intron_variant	Intron 27 of 82	1	NM_015057.5	ENSP00000444596.2

Frequencies

GnomAD3 genomes AF: 0.0964 AC: 14656 AN: 152112 Hom.: 948 Cov.: 32

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

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

GnomAD4 genome AF: 0.0965 AC: 14688 AN: 152230 Hom.: 952 Cov.: 32 AF XY: 0.0964 AC XY: 7172 AN XY: 74422

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: 36 AN: 294

European-Non Finnish (NFE) AF: 0.0621 AC: 4224 AN: 67988

Other (OTH) AF: 0.0870 AC: 184 AN: 2116

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.9
DANN	Benign	0.77
PhyloP100		-0.30
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1041242; hg19: chr13-77768172;