NM_014520.4:c.1023+9T>C

Variant names:

• chr17-4551871-A-G
• rs3816686
• NM_014520.4:c.1023+9T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014520.4(MYBBP1A):​c.1023+9T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 1,609,522 control chromosomes in the GnomAD database, including 43,069 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.20 (3701 hom., cov: 34)
  • Exomes 𝑓: 0.22 (39368 hom.)
• Consequence: MYBBP1A NM_014520.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.62
• Publications: 14 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 (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.529 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYBBP1A	NM_014520.4	c.1023+9T>C		intron_variant	Intron 8 of 25	ENST00000254718.9	NP_055335.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYBBP1A	ENST00000254718.9	c.1023+9T>C		intron_variant	Intron 8 of 25	1	NM_014520.4	ENSP00000254718.4
MYBBP1A	ENST00000573116.5	c.780+9T>C		intron_variant	Intron 7 of 25	1		ENSP00000458919.1
MYBBP1A	ENST00000381556.6	c.1023+9T>C		intron_variant	Intron 8 of 26	5		ENSP00000370968.2

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30639 AN: 152078 Hom.: 3682 Cov.: 34

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.290

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.545

Gnomad SAS AF: 0.304

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.197

Gnomad OTH AF: 0.205

GnomAD2 exomes AF: 0.249 AC: 62146 AN: 249092 AF XY: 0.247

Gnomad AFR exome AF: 0.122

Gnomad AMR exome AF: 0.347

Gnomad ASJ exome AF: 0.135

Gnomad EAS exome AF: 0.548

Gnomad FIN exome AF: 0.207

Gnomad NFE exome AF: 0.195

Gnomad OTH exome AF: 0.243

GnomAD4 exome AF: 0.220 AC: 321075 AN: 1457326 Hom.: 39368 Cov.: 31 AF XY: 0.222 AC XY: 160706 AN XY: 725204

African (AFR) AF: 0.125 AC: 4178 AN: 33400

American (AMR) AF: 0.341 AC: 15228 AN: 44600

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 3580 AN: 26116

East Asian (EAS) AF: 0.563 AC: 22336 AN: 39654

South Asian (SAS) AF: 0.297 AC: 25500 AN: 85986

European-Finnish (FIN) AF: 0.205 AC: 10856 AN: 52924

Middle Eastern (MID) AF: 0.222 AC: 1179 AN: 5316

European-Non Finnish (NFE) AF: 0.202 AC: 224591 AN: 1109126

Other (OTH) AF: 0.226 AC: 13627 AN: 60204

GnomAD4 genome AF: 0.201 AC: 30666 AN: 152196 Hom.: 3701 Cov.: 34 AF XY: 0.207 AC XY: 15389 AN XY: 74406

African (AFR) AF: 0.127 AC: 5285 AN: 41558

American (AMR) AF: 0.291 AC: 4445 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.133 AC: 461 AN: 3472

East Asian (EAS) AF: 0.546 AC: 2810 AN: 5150

South Asian (SAS) AF: 0.305 AC: 1472 AN: 4826

European-Finnish (FIN) AF: 0.209 AC: 2213 AN: 10586

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.197 AC: 13401 AN: 67984

Other (OTH) AF: 0.212 AC: 448 AN: 2114

Alfa AF: 0.205 Hom.: 7038

Bravo AF: 0.207

Asia WGS AF: 0.427 AC: 1482 AN: 3478

EpiCase AF: 0.191

EpiControl AF: 0.192

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.043
DANN	Benign	0.22
PhyloP100		-1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	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: rs3816686; hg19: chr17-4455166; COSMIC: COSV54595733; COSMIC: COSV54595733;