17-4539684-G-C

Variant names:

• chr17-4539684-G-C
• rs775880167
• NM_014520.4:c.3718C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014520.4(MYBBP1A):​c.3718C>G​(p.Arg1240Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,456,806 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1240W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: MYBBP1A NM_014520.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.93
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.043310165).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014520.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYBBP1A	NM_014520.4	MANE Select	c.3718C>G	p.Arg1240Gly	missense	Exon 26 of 26	NP_055335.2	Q9BQG0-1
	MYBBP1A	NM_001105538.2		c.3718C>G	p.Arg1240Gly	missense	Exon 26 of 27	NP_001099008.1	Q9BQG0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYBBP1A	ENST00000254718.9	TSL:1 MANE Select	c.3718C>G	p.Arg1240Gly	missense	Exon 26 of 26	ENSP00000254718.4	Q9BQG0-1
	MYBBP1A	ENST00000573116.5	TSL:1	c.3475C>G	p.Arg1159Gly	missense	Exon 25 of 26	ENSP00000458919.1	I3L1L3
	MYBBP1A	ENST00000574547.5	TSL:1	n.1286C>G		non_coding_transcript_exon	Exon 8 of 8

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1456806 Hom.: 0 Cov.: 37 AF XY: 0.00000138 AC XY: 1 AN XY: 723924

African (AFR) AF: 0.00 AC: 0 AN: 33126

American (AMR) AF: 0.00 AC: 0 AN: 44242

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26040

East Asian (EAS) AF: 0.00 AC: 0 AN: 39592

South Asian (SAS) AF: 0.00 AC: 0 AN: 86110

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53296

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5738

European-Non Finnish (NFE) AF: 9.02e-7 AC: 1 AN: 1108532

Other (OTH) AF: 0.00 AC: 0 AN: 60130

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	0.35
DANN	Benign	0.67
DEOGEN2	Benign	0.028	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.26	T
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.043	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-1.9
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.32	N
REVEL	Benign	0.029
Sift	Benign	0.23	T
Sift4G	Benign	0.41	T
Polyphen		0.0	B
Vest4		0.12
MutPred		0.26		Loss of MoRF binding (P = 0.0129)
MVP		0.33
ClinPred		0.085	T
GERP RS		-4.9
Varity_R		0.064
gMVP		0.058
Mutation Taster		=100/0	polymorphism

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: rs775880167; hg19: chr17-4442979;