rs3809849

Positions:

• chr17-4555303-G-C
• chr17-4555303-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_014520.4(MYBBP1A):​c.22C>G​(p.Gln8Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 1,603,622 control chromosomes in the GnomAD database, including 40,009 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.22 (3524 hom., cov: 34)
  • Exomes 𝑓: 0.22 (36485 hom.)
• Consequence: MYBBP1A NM_014520.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.383

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]

MYBBP1A (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00399068).
• BP6: Variant 17-4555303-G-C is Benign according to our data. Variant chr17-4555303-G-C is described in ClinVar as [Benign]. Clinvar id is 1182089.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYBBP1A	NM_014520.4	c.22C>G	p.Gln8Glu	missense_variant	1/26	ENST00000254718.9	NP_055335.2
MYBBP1A	NM_001105538.2	c.22C>G	p.Gln8Glu	missense_variant	1/27		NP_001099008.1
MYBBP1A	XM_024450536.2	c.22C>G	p.Gln8Glu	missense_variant	1/25		XP_024306304.1
MYBBP1A	XM_047435119.1	c.22C>G	p.Gln8Glu	missense_variant	1/17		XP_047291075.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYBBP1A	ENST00000254718.9	c.22C>G	p.Gln8Glu	missense_variant	1/26	1	NM_014520.4	ENSP00000254718.4
MYBBP1A	ENST00000381556.6	c.22C>G	p.Gln8Glu	missense_variant	1/27	5		ENSP00000370968.2
MYBBP1A	ENST00000570986.1	n.56C>G		non_coding_transcript_exon_variant	1/6	2

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32816 AN: 152172 Hom.: 3519 Cov.: 34

Gnomad AFR AF: 0.237

Gnomad AMI AF: 0.343

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.208

GnomAD3 exomes AF: 0.209 AC: 47640 AN: 228244 Hom.: 4943 AF XY: 0.210 AC XY: 26261 AN XY: 124826

Gnomad AFR exome AF: 0.235

Gnomad AMR exome AF: 0.176

Gnomad ASJ exome AF: 0.146

Gnomad EAS exome AF: 0.144

Gnomad SAS exome AF: 0.236

Gnomad FIN exome AF: 0.209

Gnomad NFE exome AF: 0.225

Gnomad OTH exome AF: 0.203

GnomAD4 exome AF: 0.223 AC: 323191 AN: 1451332 Hom.: 36485 Cov.: 35 AF XY: 0.222 AC XY: 159982 AN XY: 721276

Gnomad4 AFR exome AF: 0.234

Gnomad4 AMR exome AF: 0.176

Gnomad4 ASJ exome AF: 0.150

Gnomad4 EAS exome AF: 0.171

Gnomad4 SAS exome AF: 0.235

Gnomad4 FIN exome AF: 0.213

Gnomad4 NFE exome AF: 0.228

Gnomad4 OTH exome AF: 0.209

GnomAD4 genome AF: 0.216 AC: 32855 AN: 152290 Hom.: 3524 Cov.: 34 AF XY: 0.214 AC XY: 15953 AN XY: 74466

Gnomad4 AFR AF: 0.237

Gnomad4 AMR AF: 0.169

Gnomad4 ASJ AF: 0.166

Gnomad4 EAS AF: 0.151

Gnomad4 SAS AF: 0.239

Gnomad4 FIN AF: 0.207

Gnomad4 NFE AF: 0.220

Gnomad4 OTH AF: 0.209

Alfa AF: 0.182 Hom.: 912

Bravo AF: 0.215

TwinsUK AF: 0.213 AC: 788

ALSPAC AF: 0.227 AC: 873

ESP6500AA AF: 0.230 AC: 1012

ESP6500EA AF: 0.207 AC: 1775

ExAC AF: 0.200 AC: 24008

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 29, 2020	This variant is associated with the following publications: (PMID: 23129390) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.053
BayesDel_addAF	Benign	-0.81	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.46
DANN	Benign	0.66
DEOGEN2	Benign	0.021	.;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0027	N
LIST_S2	Benign	0.30	T;T
MetaRNN	Benign	0.0040	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-1.5	N;N
PrimateAI	Benign	0.40	T
PROVEAN	Benign	0.52	N;N
REVEL	Benign	0.14
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;B
Vest4		0.027
ClinPred		0.0077	T
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.046
gMVP		0.15

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: rs3809849; hg19: chr17-4458598; COSMIC: COSV54595359; COSMIC: COSV54595359;