chr13-77055554-A-T

Variant names:

• chr13-77055554-A-T
• rs200563433
• NM_015057.5:c.13647+4T>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_015057.5(MYCBP2):​c.13647+4T>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00262 in 1,612,264 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0024 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0026 (6 hom.)
• Consequence: MYCBP2 NM_015057.5 splice_region, intron
• Scores: Splicing: ADA: 0.0001324
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 1.22
• Publications: 0 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]

ENSG00000283208 (HGNC:):

MYCBP2-AS1 (HGNC:41023): (MYCBP2 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 13-77055554-A-T is Benign according to our data. Variant chr13-77055554-A-T is described in ClinVar as Likely_benign. ClinVar VariationId is 718182.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 364 AD gene.

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.13647+4T>A		splice_region intron	N/A	NP_055872.4	O75592-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYCBP2	ENST00000544440.7	TSL:1 MANE Select	c.13647+4T>A		splice_region intron	N/A	ENSP00000444596.2	O75592-1
	MYCBP2	ENST00000357337.11	TSL:1	c.13827+4T>A		splice_region intron	N/A	ENSP00000349892.6	A0A499FJI4
	ENSG00000283208	ENST00000638147.2	TSL:5	c.566-19964A>T		intron	N/A	ENSP00000490953.2	A0A1B0GWJ7

Frequencies

GnomAD3 genomes AF: 0.00239 AC: 364 AN: 152188 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00177

Gnomad ASJ AF: 0.00433

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.00104

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00419

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.00220 AC: 546 AN: 248350 AF XY: 0.00222

Gnomad AFR exome AF: 0.000308

Gnomad AMR exome AF: 0.00110

Gnomad ASJ exome AF: 0.00428

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00178

Gnomad NFE exome AF: 0.00360

Gnomad OTH exome AF: 0.00198

GnomAD4 exome AF: 0.00264 AC: 3858 AN: 1459958 Hom.: 6 Cov.: 30 AF XY: 0.00262 AC XY: 1901 AN XY: 726344

African (AFR) AF: 0.000359 AC: 12 AN: 33458

American (AMR) AF: 0.00107 AC: 48 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.00387 AC: 101 AN: 26098

East Asian (EAS) AF: 0.00 AC: 0 AN: 39650

South Asian (SAS) AF: 0.000569 AC: 49 AN: 86104

European-Finnish (FIN) AF: 0.00187 AC: 99 AN: 52956

Middle Eastern (MID) AF: 0.00121 AC: 7 AN: 5762

European-Non Finnish (NFE) AF: 0.00305 AC: 3389 AN: 1110906

Other (OTH) AF: 0.00254 AC: 153 AN: 60340

GnomAD4 genome AF: 0.00239 AC: 364 AN: 152306 Hom.: 0 Cov.: 32 AF XY: 0.00213 AC XY: 159 AN XY: 74476

African (AFR) AF: 0.000481 AC: 20 AN: 41576

American (AMR) AF: 0.00177 AC: 27 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00433 AC: 15 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000830 AC: 4 AN: 4822

European-Finnish (FIN) AF: 0.00104 AC: 11 AN: 10622

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00419 AC: 285 AN: 68030

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.00319 Hom.: 0

Bravo AF: 0.00234

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00289

EpiControl AF: 0.00350

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	MYCBP2-related disorder (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	16
DANN	Benign	0.69
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00013
dbscSNV1_RF	Benign	0.048
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: rs200563433; hg19: chr13-77629689;