rs10488699

Variant names:

• chr11-116761784-C-T
• rs10488699
• NM_032725.4:c.1036+769G>A

Variant summary

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

The NM_032725.4(BUD13):​c.1036+769G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0973 in 152,196 control chromosomes in the GnomAD database, including 890 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 0.097 (890 hom., cov: 33)
• Consequence: BUD13 NM_032725.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.06
• Publications: 14 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.16 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BUD13	NM_032725.4	MANE Select	c.1036+769G>A		intron	N/A	NP_116114.1
	BUD13	NM_001159736.2		c.635-832G>A		intron	N/A	NP_001153208.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BUD13	ENST00000260210.5	TSL:1 MANE Select	c.1036+769G>A		intron	N/A	ENSP00000260210.3
	BUD13	ENST00000375445.7	TSL:1	c.635-832G>A		intron	N/A	ENSP00000364594.3
	BUD13	ENST00000419189.1	TSL:5	n.283+769G>A		intron	N/A	ENSP00000415748.1

Frequencies

GnomAD3 genomes AF: 0.0971 AC: 14766 AN: 152078 Hom.: 886 Cov.: 33

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.0709

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0459

Gnomad FIN AF: 0.0603

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0675

Gnomad OTH AF: 0.105

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

GnomAD4 genome AF: 0.0973 AC: 14802 AN: 152196 Hom.: 890 Cov.: 33 AF XY: 0.0965 AC XY: 7179 AN XY: 74422

African (AFR) AF: 0.163 AC: 6777 AN: 41514

American (AMR) AF: 0.129 AC: 1965 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0709 AC: 246 AN: 3472

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5186

South Asian (SAS) AF: 0.0462 AC: 223 AN: 4828

European-Finnish (FIN) AF: 0.0603 AC: 639 AN: 10604

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0675 AC: 4591 AN: 67998

Other (OTH) AF: 0.104 AC: 220 AN: 2112

Alfa AF: 0.108 Hom.: 346

Bravo AF: 0.105

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
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.0
DANN	Benign	0.81
PhyloP100		-2.1
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: rs10488699; hg19: chr11-116632500;