rs62620242

chr17-4539636-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM4 BP6_Moderate BS2

The NM_014520.4(MYBBP1A):c.3766C>T(p.Gln1256Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000386 in 1,612,882 control chromosomes in the GnomAD database, including 4 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0021 (3 hom., cov: 31)
  • Exomes 𝑓: 0.00021 (1 hom.)
• Consequence: MYBBP1A NM_014520.4 stop_gained
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.96

Genes affected

MYBBP1A (HGNC:7546): (MYB binding protein 1a) This gene encodes a nucleolar transcriptional regulator that was first identified by its ability to bind specifically to the Myb proto-oncogene protein. The encoded protein is thought to play a role in many cellular processes including response to nucleolar stress, tumor suppression and synthesis of ribosomal DNA. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM4: Stoplost variant in NM_014520.4 Downstream stopcodon found after 21 codons.
• BP6: Variant 17-4539636-G-A is Benign according to our data. Variant chr17-4539636-G-A is described in ClinVar as [Benign]. Clinvar id is 715079.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 314 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYBBP1A	NM_014520.4	c.3766C>T	p.Gln1256Ter	stop_gained	26/26	ENST00000254718.9
MYBBP1A	NM_001105538.2	c.3766C>T	p.Gln1256Ter	stop_gained	26/27
MYBBP1A	XM_011523616.3	c.3010C>T	p.Gln1004Ter	stop_gained	21/21
MYBBP1A	XM_024450536.2	c.*266C>T		3_prime_UTR_variant	25/25

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYBBP1A	ENST00000254718.9	c.3766C>T	p.Gln1256Ter	stop_gained	26/26	1	NM_014520.4	P2

Frequencies

GnomAD3 genomes AF: 0.00206 AC: 314 AN: 152066 Hom.: 3 Cov.: 31

Gnomad AFR AF: 0.00700

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.000601 AC: 151 AN: 251230 Hom.: 1 AF XY: 0.000479 AC XY: 65 AN XY: 135802

Gnomad AFR exome AF: 0.00795

Gnomad AMR exome AF: 0.000550

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000327

GnomAD4 exome AF: 0.000208 AC: 304 AN: 1460698 Hom.: 1 Cov.: 37 AF XY: 0.000157 AC XY: 114 AN XY: 726458

Gnomad4 AFR exome AF: 0.00734

Gnomad4 AMR exome AF: 0.000538

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000540

Gnomad4 OTH exome AF: 0.000414

GnomAD4 genome AF: 0.00209 AC: 318 AN: 152184 Hom.: 3 Cov.: 31 AF XY: 0.00194 AC XY: 144 AN XY: 74388

Gnomad4 AFR AF: 0.00708

Gnomad4 AMR AF: 0.00131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.000417 Hom.: 0

Bravo AF: 0.00244

ESP6500AA AF: 0.00749 AC: 33

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000675 AC: 82

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.044	T
BayesDel_noAF	Pathogenic	0.29
Cadd	Pathogenic	36
Dann	Uncertain	0.99
Eigen	Uncertain	0.22
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.18	N
MutationTaster	Benign	1.0	A;D
Vest4		0.58
GERP RS		2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs62620242; hg19: chr17-4442931; COSMIC: COSV104543380; COSMIC: COSV104543380;