11-116769521-A-G

Variant names:

• chr11-116769521-A-G
• rs6589565
• NM_032725.4:c.237+608T>C

Variant summary

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

The NM_032725.4(BUD13):​c.237+608T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.929 in 152,280 control chromosomes in the GnomAD database, including 65,963 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 0.93 (65963 hom., cov: 32)
• Consequence: BUD13 NM_032725.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0800
• Publications: 16 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.976 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.237+608T>C		intron	N/A	NP_116114.1	Q9BRD0-1
	BUD13	NM_001159736.2		c.237+608T>C		intron	N/A	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.237+608T>C		intron	N/A	ENSP00000260210.3	Q9BRD0-1
	BUD13	ENST00000375445.7	TSL:1	c.237+608T>C		intron	N/A	ENSP00000364594.3	Q9BRD0-2
	BUD13	ENST00000911264.1		c.234+611T>C		intron	N/A	ENSP00000581323.1

Frequencies

GnomAD3 genomes AF: 0.929 AC: 141360 AN: 152162 Hom.: 65912 Cov.: 32

Gnomad AFR AF: 0.984

Gnomad AMI AF: 0.897

Gnomad AMR AF: 0.886

Gnomad ASJ AF: 0.910

Gnomad EAS AF: 0.772

Gnomad SAS AF: 0.809

Gnomad FIN AF: 0.918

Gnomad MID AF: 0.889

Gnomad NFE AF: 0.929

Gnomad OTH AF: 0.919

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

GnomAD4 genome AF: 0.929 AC: 141467 AN: 152280 Hom.: 65963 Cov.: 32 AF XY: 0.925 AC XY: 68913 AN XY: 74464

African (AFR) AF: 0.984 AC: 40911 AN: 41558

American (AMR) AF: 0.886 AC: 13550 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.910 AC: 3159 AN: 3472

East Asian (EAS) AF: 0.771 AC: 3993 AN: 5176

South Asian (SAS) AF: 0.808 AC: 3899 AN: 4824

European-Finnish (FIN) AF: 0.918 AC: 9735 AN: 10600

Middle Eastern (MID) AF: 0.895 AC: 263 AN: 294

European-Non Finnish (NFE) AF: 0.929 AC: 63210 AN: 68038

Other (OTH) AF: 0.914 AC: 1929 AN: 2110

Alfa AF: 0.952 Hom.: 16794

Bravo AF: 0.929

Asia WGS AF: 0.805 AC: 2803 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.2
DANN	Benign	0.59
PhyloP100		0.080
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: rs6589565; hg19: chr11-116640237;