11-116760675-T-C

Position:

• chr11-116760675-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032725.4(BUD13):​c.1254+60A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 1,529,136 control chromosomes in the GnomAD database, including 133,748 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 0.33 (9403 hom., cov: 32)
  • Exomes 𝑓: 0.42 (124345 hom.)
• Consequence: BUD13 NM_032725.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.143

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.439 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BUD13	NM_032725.4	c.1254+60A>G		intron_variant		ENST00000260210.5	NP_116114.1
BUD13	NM_001159736.2	c.852+60A>G		intron_variant			NP_001153208.1
BUD13	XM_011543035.3	c.1155+60A>G		intron_variant			XP_011541337.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BUD13	ENST00000260210.5	c.1254+60A>G		intron_variant		1	NM_032725.4	ENSP00000260210	P2
BUD13	ENST00000375445.7	c.852+60A>G		intron_variant		1		ENSP00000364594	A2
BUD13	ENST00000419189.1	c.284+1878A>G		intron_variant, NMD_transcript_variant		5		ENSP00000415748

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49571 AN: 151914 Hom.: 9410 Cov.: 32

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.394

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.402

Gnomad EAS AF: 0.282

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.299

Gnomad NFE AF: 0.443

Gnomad OTH AF: 0.332

GnomAD3 exomes AF: 0.348 AC: 86279 AN: 247860 Hom.: 16496 AF XY: 0.354 AC XY: 47508 AN XY: 134352

Gnomad AFR exome AF: 0.142

Gnomad AMR exome AF: 0.222

Gnomad ASJ exome AF: 0.404

Gnomad EAS exome AF: 0.283

Gnomad SAS exome AF: 0.264

Gnomad FIN exome AF: 0.362

Gnomad NFE exome AF: 0.441

Gnomad OTH exome AF: 0.376

GnomAD4 exome AF: 0.415 AC: 571808 AN: 1377104 Hom.: 124345 Cov.: 21 AF XY: 0.410 AC XY: 283261 AN XY: 690090

Gnomad4 AFR exome AF: 0.139

Gnomad4 AMR exome AF: 0.229

Gnomad4 ASJ exome AF: 0.401

Gnomad4 EAS exome AF: 0.249

Gnomad4 SAS exome AF: 0.267

Gnomad4 FIN exome AF: 0.364

Gnomad4 NFE exome AF: 0.455

Gnomad4 OTH exome AF: 0.387

GnomAD4 genome AF: 0.326 AC: 49559 AN: 152032 Hom.: 9403 Cov.: 32 AF XY: 0.318 AC XY: 23595 AN XY: 74312

Gnomad4 AFR AF: 0.150

Gnomad4 AMR AF: 0.273

Gnomad4 ASJ AF: 0.402

Gnomad4 EAS AF: 0.281

Gnomad4 SAS AF: 0.262

Gnomad4 FIN AF: 0.362

Gnomad4 NFE AF: 0.443

Gnomad4 OTH AF: 0.328

Alfa AF: 0.417 Hom.: 26025

Bravo AF: 0.314

Asia WGS AF: 0.243 AC: 846 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.4
DANN	Benign	0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3741301; hg19: chr11-116631391; COSMIC: COSV52768149;