rs11820589

Variant names:

• chr11-116763146-G-A
• rs11820589
• NM_032725.4:c.443C>T

Variant summary

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

The NM_032725.4(BUD13):​c.443C>T​(p.Pro148Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0719 in 1,599,516 control chromosomes in the GnomAD database, including 4,944 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 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 0.099 (945 hom., cov: 32)
  • Exomes 𝑓: 0.069 (3999 hom.)
• Consequence: BUD13 NM_032725.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.04
• Publications: 62 publications found

Genes affected

BUD13 (HGNC:28199): (BUD13 homolog) Enables RNA binding activity. Involved in mRNA splicing, via spliceosome. Located in nucleoplasm. Part of U2-type precatalytic spliceosome. [provided by Alliance of Genome Resources, Apr 2022]

BUD13 Gene-Disease associations (from GenCC):

• progeroid syndrome

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000308823 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.0017516613).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032725.4. 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
	BUD13	NM_032725.4	MANE Select	c.443C>T	p.Pro148Leu	missense	Exon 4 of 10	NP_116114.1	Q9BRD0-1
	BUD13	NM_001159736.2		c.443C>T	p.Pro148Leu	missense	Exon 4 of 10	NP_001153208.1	Q9BRD0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BUD13	ENST00000260210.5	TSL:1 MANE Select	c.443C>T	p.Pro148Leu	missense	Exon 4 of 10	ENSP00000260210.3	Q9BRD0-1
	BUD13	ENST00000375445.7	TSL:1	c.443C>T	p.Pro148Leu	missense	Exon 4 of 10	ENSP00000364594.3	Q9BRD0-2
	BUD13	ENST00000911264.1		c.440C>T	p.Pro147Leu	missense	Exon 4 of 10	ENSP00000581323.1

Frequencies

GnomAD3 genomes AF: 0.0987 AC: 14989 AN: 151892 Hom.: 941 Cov.: 32

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.0709

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0456

Gnomad FIN AF: 0.0603

Gnomad MID AF: 0.0796

Gnomad NFE AF: 0.0673

Gnomad OTH AF: 0.104

GnomAD2 exomes AF: 0.0784 AC: 19391 AN: 247394 AF XY: 0.0724

Gnomad AFR exome AF: 0.168

Gnomad AMR exome AF: 0.156

Gnomad ASJ exome AF: 0.0703

Gnomad EAS exome AF: 0.000326

Gnomad FIN exome AF: 0.0660

Gnomad NFE exome AF: 0.0674

Gnomad OTH exome AF: 0.0745

GnomAD4 exome AF: 0.0691 AC: 99955 AN: 1447506 Hom.: 3999 Cov.: 34 AF XY: 0.0675 AC XY: 48586 AN XY: 719624

African (AFR) AF: 0.174 AC: 5772 AN: 33244

American (AMR) AF: 0.153 AC: 6767 AN: 44300

Ashkenazi Jewish (ASJ) AF: 0.0683 AC: 1747 AN: 25580

East Asian (EAS) AF: 0.000558 AC: 22 AN: 39452

South Asian (SAS) AF: 0.0438 AC: 3733 AN: 85318

European-Finnish (FIN) AF: 0.0682 AC: 3620 AN: 53058

Middle Eastern (MID) AF: 0.0620 AC: 354 AN: 5708

European-Non Finnish (NFE) AF: 0.0670 AC: 73728 AN: 1100976

Other (OTH) AF: 0.0704 AC: 4212 AN: 59870

GnomAD4 genome AF: 0.0988 AC: 15026 AN: 152010 Hom.: 945 Cov.: 32 AF XY: 0.0980 AC XY: 7285 AN XY: 74306

African (AFR) AF: 0.171 AC: 7100 AN: 41454

American (AMR) AF: 0.124 AC: 1898 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0709 AC: 246 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5176

South Asian (SAS) AF: 0.0458 AC: 221 AN: 4822

European-Finnish (FIN) AF: 0.0603 AC: 640 AN: 10610

Middle Eastern (MID) AF: 0.0856 AC: 25 AN: 292

European-Non Finnish (NFE) AF: 0.0673 AC: 4567 AN: 67880

Other (OTH) AF: 0.103 AC: 218 AN: 2110

Alfa AF: 0.0749 Hom.: 1603

Bravo AF: 0.107

TwinsUK AF: 0.0658 AC: 244

ALSPAC AF: 0.0690 AC: 266

ESP6500AA AF: 0.165 AC: 725

ESP6500EA AF: 0.0682 AC: 586

ExAC AF: 0.0766 AC: 9293

Asia WGS AF: 0.0400 AC: 140 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	20
DANN	Benign	0.93
DEOGEN2	Benign	0.026	T
Eigen	Benign	-0.0077
Eigen_PC	Benign	-0.0029
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.91	D
MetaRNN	Benign	0.0018	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		5.0
PrimateAI	Benign	0.41	T
PROVEAN	Pathogenic	-5.4	D
REVEL	Benign	0.17
Sift	Uncertain	0.0020	D
Sift4G	Benign	0.12	T
Polyphen		0.73	P
Vest4		0.21
MPC		0.10
ClinPred		0.094	T
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.094
gMVP		0.17
Mutation Taster		=92/8	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: rs11820589; hg19: chr11-116633862; COSMIC: COSV107279482; COSMIC: COSV107279482;