17-4539506-T-C

Position:

• chr17-4539506-T-C

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.3896A>G​(p.Lys1299Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00388 in 1,614,096 control chromosomes in the GnomAD database, including 198 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 (★★).

• Frequency:
  • Genomes: 𝑓 0.021 (106 hom., cov: 31)
  • Exomes 𝑓: 0.0021 (92 hom.)
• Consequence: MYBBP1A NM_014520.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.566

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=0.0017130971).
• BP6: Variant 17-4539506-T-C is Benign according to our data. Variant chr17-4539506-T-C is described in ClinVar as [Benign]. Clinvar id is 768823.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0698 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYBBP1A	NM_014520.4	c.3896A>G	p.Lys1299Arg	missense_variant	26/26	ENST00000254718.9	NP_055335.2
MYBBP1A	NM_001105538.2	c.3896A>G	p.Lys1299Arg	missense_variant	26/27		NP_001099008.1
MYBBP1A	XM_011523616.3	c.3140A>G	p.Lys1047Arg	missense_variant	21/21		XP_011521918.1
MYBBP1A	XM_024450536.2	c.*396A>G		3_prime_UTR_variant	25/25		XP_024306304.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYBBP1A	ENST00000254718.9	c.3896A>G	p.Lys1299Arg	missense_variant	26/26	1	NM_014520.4	ENSP00000254718.4

Frequencies

GnomAD3 genomes AF: 0.0206 AC: 3140 AN: 152110 Hom.: 103 Cov.: 31

Gnomad AFR AF: 0.0717

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00694

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000397

Gnomad OTH AF: 0.0148

GnomAD3 exomes AF: 0.00570 AC: 1433 AN: 251454 Hom.: 52 AF XY: 0.00441 AC XY: 599 AN XY: 135900

Gnomad AFR exome AF: 0.0749

Gnomad AMR exome AF: 0.00437

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000343

Gnomad OTH exome AF: 0.00309

GnomAD4 exome AF: 0.00212 AC: 3105 AN: 1461868 Hom.: 92 Cov.: 37 AF XY: 0.00182 AC XY: 1326 AN XY: 727238

Gnomad4 AFR exome AF: 0.0706

Gnomad4 AMR exome AF: 0.00454

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000301

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000170

Gnomad4 OTH exome AF: 0.00490

GnomAD4 genome AF: 0.0208 AC: 3159 AN: 152228 Hom.: 106 Cov.: 31 AF XY: 0.0203 AC XY: 1508 AN XY: 74440

Gnomad4 AFR AF: 0.0720

Gnomad4 AMR AF: 0.00693

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000397

Gnomad4 OTH AF: 0.0147

Alfa AF: 0.00367 Hom.: 31

Bravo AF: 0.0238

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0665 AC: 293

ESP6500EA AF: 0.000581 AC: 5

ExAC AF: 0.00689 AC: 836

Asia WGS AF: 0.00577 AC: 20 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.000474

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	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	5.1
DANN	Benign	0.79
DEOGEN2	Benign	0.051	.;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.063	N
LIST_S2	Benign	0.67	T;T
MetaRNN	Benign	0.0017	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.79	N;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.50	N;N
REVEL	Benign	0.011
Sift	Benign	0.49	T;T
Sift4G	Benign	0.44	T;T
Polyphen		0.037	B;B
Vest4		0.18
MVP		0.58
ClinPred		0.00048	T
GERP RS		0.16
Varity_R		0.028
gMVP		0.032

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: rs78578064; hg19: chr17-4442801;