rs17119975

Variant names:

• chr11-116763841-T-C
• rs17119975
• NM_032725.4:c.323-575A>G

Variant summary

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

The NM_032725.4(BUD13):​c.323-575A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 152,244 control chromosomes in the GnomAD database, including 1,582 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 0.13 (1582 hom., cov: 32)
• Consequence: BUD13 NM_032725.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.453
• Publications: 13 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 (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BUD13	NM_032725.4	c.323-575A>G		intron_variant	Intron 3 of 9	ENST00000260210.5	NP_116114.1
BUD13	NM_001159736.2	c.323-575A>G		intron_variant	Intron 3 of 9		NP_001153208.1
BUD13	XM_011543035.3	c.224-575A>G		intron_variant	Intron 3 of 9		XP_011541337.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BUD13	ENST00000260210.5	c.323-575A>G		intron_variant	Intron 3 of 9	1	NM_032725.4	ENSP00000260210.3
BUD13	ENST00000375445.7	c.323-575A>G		intron_variant	Intron 3 of 9	1		ENSP00000364594.3
ENSG00000308823	ENST00000836679.1	n.434-1409T>C		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19185 AN: 152126 Hom.: 1582 Cov.: 32

Gnomad AFR AF: 0.0482

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.288

Gnomad FIN AF: 0.185

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.103

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.126 AC: 19193 AN: 152244 Hom.: 1582 Cov.: 32 AF XY: 0.132 AC XY: 9846 AN XY: 74436

African (AFR) AF: 0.0481 AC: 1999 AN: 41570

American (AMR) AF: 0.149 AC: 2276 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 416 AN: 3470

East Asian (EAS) AF: 0.216 AC: 1118 AN: 5180

South Asian (SAS) AF: 0.288 AC: 1387 AN: 4822

European-Finnish (FIN) AF: 0.185 AC: 1957 AN: 10590

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.143 AC: 9756 AN: 68010

Other (OTH) AF: 0.106 AC: 225 AN: 2114

Alfa AF: 0.115 Hom.: 405

Bravo AF: 0.116

Asia WGS AF: 0.231 AC: 804 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.3
DANN	Benign	0.61
PhyloP100		0.45
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: rs17119975; hg19: chr11-116634557;