chr17-4539780-T-A

Variant names:

• chr17-4539780-T-A
• rs9905742
• NM_014520.4:c.3622A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_014520.4(MYBBP1A):​c.3622A>T​(p.Met1208Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0331 in 1,612,762 control chromosomes in the GnomAD database, including 1,091 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.027 (84 hom., cov: 31)
  • Exomes 𝑓: 0.034 (1007 hom.)
• Consequence: MYBBP1A NM_014520.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0910
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0017639995).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0271 (4118/152202) while in subpopulation NFE AF = 0.0393 (2675/67996). AF 95% confidence interval is 0.0381. There are 84 homozygotes in GnomAd4. There are 1942 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 4118 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYBBP1A	NM_014520.4	c.3622A>T	p.Met1208Leu	missense_variant	Exon 26 of 26	ENST00000254718.9	NP_055335.2
MYBBP1A	NM_001105538.2	c.3622A>T	p.Met1208Leu	missense_variant	Exon 26 of 27		NP_001099008.1
MYBBP1A	XM_011523616.3	c.2866A>T	p.Met956Leu	missense_variant	Exon 21 of 21		XP_011521918.1
MYBBP1A	XM_024450536.2	c.*122A>T		3_prime_UTR_variant	Exon 25 of 25		XP_024306304.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYBBP1A	ENST00000254718.9	c.3622A>T	p.Met1208Leu	missense_variant	Exon 26 of 26	1	NM_014520.4	ENSP00000254718.4

Frequencies

GnomAD3 genomes AF: 0.0271 AC: 4120 AN: 152084 Hom.: 85 Cov.: 31

Gnomad AFR AF: 0.00664

Gnomad AMI AF: 0.0363

Gnomad AMR AF: 0.0340

Gnomad ASJ AF: 0.0824

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0220

Gnomad FIN AF: 0.0122

Gnomad MID AF: 0.0510

Gnomad NFE AF: 0.0394

Gnomad OTH AF: 0.0369

GnomAD2 exomes AF: 0.0305 AC: 7632 AN: 250574 AF XY: 0.0315

Gnomad AFR exome AF: 0.00425

Gnomad AMR exome AF: 0.0264

Gnomad ASJ exome AF: 0.0801

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.0126

Gnomad NFE exome AF: 0.0400

Gnomad OTH exome AF: 0.0364

GnomAD4 exome AF: 0.0337 AC: 49191 AN: 1460560 Hom.: 1007 Cov.: 37 AF XY: 0.0341 AC XY: 24794 AN XY: 726664

African (AFR) AF: 0.00630 AC: 211 AN: 33480

American (AMR) AF: 0.0279 AC: 1249 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0829 AC: 2166 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0274 AC: 2362 AN: 86254

European-Finnish (FIN) AF: 0.0146 AC: 759 AN: 52116

Middle Eastern (MID) AF: 0.0479 AC: 276 AN: 5764

European-Non Finnish (NFE) AF: 0.0360 AC: 40079 AN: 1112002

Other (OTH) AF: 0.0346 AC: 2089 AN: 60388

GnomAD4 genome AF: 0.0271 AC: 4118 AN: 152202 Hom.: 84 Cov.: 31 AF XY: 0.0261 AC XY: 1942 AN XY: 74428

African (AFR) AF: 0.00662 AC: 275 AN: 41526

American (AMR) AF: 0.0339 AC: 519 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0824 AC: 286 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.0224 AC: 108 AN: 4814

European-Finnish (FIN) AF: 0.0122 AC: 130 AN: 10614

Middle Eastern (MID) AF: 0.0514 AC: 15 AN: 292

European-Non Finnish (NFE) AF: 0.0393 AC: 2675 AN: 67996

Other (OTH) AF: 0.0360 AC: 76 AN: 2110

Alfa AF: 0.0401 Hom.: 110

Bravo AF: 0.0277

TwinsUK AF: 0.0334 AC: 124

ALSPAC AF: 0.0306 AC: 118

ESP6500AA AF: 0.00522 AC: 23

ESP6500EA AF: 0.0402 AC: 346

ExAC AF: 0.0303 AC: 3679

Asia WGS AF: 0.0120 AC: 41 AN: 3478

EpiCase AF: 0.0429

EpiControl AF: 0.0467

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	7.5
DANN	Benign	0.70
DEOGEN2	Benign	0.029	.;T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.62	T;T
MetaRNN	Benign	0.0018	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.0	N;N
PhyloP100		0.091
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.24	N;N
REVEL	Benign	0.082
Sift	Benign	0.031	D;D
Sift4G	Benign	1.0	T;T
Polyphen		0.0030	B;B
Vest4		0.096
MutPred		0.060		Gain of glycosylation at S1207 (P = 0.0421);Gain of glycosylation at S1207 (P = 0.0421);
ClinPred		0.0048	T
GERP RS		1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.17
gMVP		0.067
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9905742; hg19: chr17-4443075; COSMIC: COSV54598438; COSMIC: COSV54598438;