11-116768388-A-G

Variant names:

• chr11-116768388-A-G
• rs10790162
• NM_032725.4:c.237+1741T>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+1741T>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 152,252 control chromosomes in the GnomAD database, including 65,953 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 (65953 hom., cov: 32)
• Consequence: BUD13 NM_032725.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.167
• Publications: 67 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BUD13	NM_032725.4	c.237+1741T>C		intron_variant	Intron 2 of 9	ENST00000260210.5	NP_116114.1
BUD13	NM_001159736.2	c.237+1741T>C		intron_variant	Intron 2 of 9		NP_001153208.1
BUD13	XM_011543035.3	c.138+1741T>C		intron_variant	Intron 2 of 9		XP_011541337.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BUD13	ENST00000260210.5	c.237+1741T>C		intron_variant	Intron 2 of 9	1	NM_032725.4	ENSP00000260210.3
BUD13	ENST00000375445.7	c.237+1741T>C		intron_variant	Intron 2 of 9	1		ENSP00000364594.3

Frequencies

GnomAD3 genomes AF: 0.929 AC: 141338 AN: 152134 Hom.: 65902 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: 0.773

Gnomad SAS AF: 0.810

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: 141445 AN: 152252 Hom.: 65953 Cov.: 32 AF XY: 0.925 AC XY: 68896 AN XY: 74446

African (AFR) AF: 0.984 AC: 40923 AN: 41570

American (AMR) AF: 0.886 AC: 13553 AN: 15296

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

East Asian (EAS) AF: 0.772 AC: 3993 AN: 5172

South Asian (SAS) AF: 0.809 AC: 3905 AN: 4826

European-Finnish (FIN) AF: 0.918 AC: 9715 AN: 10578

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

European-Non Finnish (NFE) AF: 0.929 AC: 63182 AN: 68016

Other (OTH) AF: 0.914 AC: 1934 AN: 2116

Alfa AF: 0.923 Hom.: 198054

Bravo AF: 0.929

Asia WGS AF: 0.804 AC: 2782 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	3.2
DANN	Benign	0.73
PhyloP100		0.17
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: rs10790162; hg19: chr11-116639104;