13-77305241-G-A

Position:

• chr13-77305241-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015057.5(MYCBP2):​c.303-8567C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 151,960 control chromosomes in the GnomAD database, including 2,334 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 0.16 (2334 hom., cov: 32)
• Consequence: MYCBP2 NM_015057.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.495

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 (HGNC:):

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 (SAS) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYCBP2	NM_015057.5	c.303-8567C>T		intron_variant		ENST00000544440.7	NP_055872.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYCBP2	ENST00000544440.7	c.303-8567C>T		intron_variant		1	NM_015057.5	ENSP00000444596.2

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24864 AN: 151840 Hom.: 2329 Cov.: 32

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.313

Gnomad SAS AF: 0.400

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.170

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.164 AC: 24875 AN: 151960 Hom.: 2334 Cov.: 32 AF XY: 0.169 AC XY: 12520 AN XY: 74264

Gnomad4 AFR AF: 0.116

Gnomad4 AMR AF: 0.122

Gnomad4 ASJ AF: 0.152

Gnomad4 EAS AF: 0.314

Gnomad4 SAS AF: 0.401

Gnomad4 FIN AF: 0.189

Gnomad4 NFE AF: 0.170

Gnomad4 OTH AF: 0.172

Alfa AF: 0.179 Hom.: 1196

Bravo AF: 0.152

Asia WGS AF: 0.362 AC: 1253 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.6
DANN	Benign	0.29

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: rs7322722; hg19: chr13-77879376;