rs1041242

chr13-77194037-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
MYCBP2	NM_015057.5	c.3935+116A>G		intron_variant		ENST00000544440.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYCBP2	ENST00000544440.7	c.3935+116A>G		intron_variant		1	NM_015057.5	A1

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

Gnomad4 AFR exome AF: 0.178

Gnomad4 AMR exome AF: 0.0717

Gnomad4 ASJ exome AF: 0.0829

Gnomad4 EAS exome AF: 0.121

Gnomad4 SAS exome AF: 0.0372

Gnomad4 FIN exome AF: 0.0709

Gnomad4 NFE exome AF: 0.0645

Gnomad4 OTH exome AF: 0.0783

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

Gnomad4 AFR AF: 0.177

Gnomad4 AMR AF: 0.0674

Gnomad4 ASJ AF: 0.0928

Gnomad4 EAS AF: 0.111

Gnomad4 SAS AF: 0.0399

Gnomad4 FIN AF: 0.0626

Gnomad4 NFE AF: 0.0621

Gnomad4 OTH AF: 0.0870

Alfa AF: 0.0719 Hom.: 176

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

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

LitVar

Other links and lift over

dbSNP: rs1041242; hg19: chr13-77768172;