11-116760675-T-C

Variant names:

• chr11-116760675-T-C
• rs3741301
• NM_032725.4:c.1254+60A>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.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
• Publications: 17 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=-0.9).
• 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 rank	MANE	Protein	UniProt
BUD13	NM_032725.4	c.1254+60A>G		intron_variant	Intron 5 of 9	ENST00000260210.5	NP_116114.1
BUD13	NM_001159736.2	c.852+60A>G		intron_variant	Intron 5 of 9		NP_001153208.1
BUD13	XM_011543035.3	c.1155+60A>G		intron_variant	Intron 5 of 9		XP_011541337.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BUD13	ENST00000260210.5	c.1254+60A>G		intron_variant	Intron 5 of 9	1	NM_032725.4	ENSP00000260210.3
BUD13	ENST00000375445.7	c.852+60A>G		intron_variant	Intron 5 of 9	1		ENSP00000364594.3
BUD13	ENST00000419189.1	n.283+1878A>G		intron_variant	Intron 1 of 3	5		ENSP00000415748.1
ENSG00000308823	ENST00000836679.1	n.434-4575T>C		intron_variant	Intron 2 of 2

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

GnomAD2 exomes AF: 0.348 AC: 86279 AN: 247860 AF XY: 0.354

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 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

African (AFR) AF: 0.139 AC: 4374 AN: 31484

American (AMR) AF: 0.229 AC: 10154 AN: 44358

Ashkenazi Jewish (ASJ) AF: 0.401 AC: 10189 AN: 25418

East Asian (EAS) AF: 0.249 AC: 9775 AN: 39244

South Asian (SAS) AF: 0.267 AC: 22394 AN: 84016

European-Finnish (FIN) AF: 0.364 AC: 19335 AN: 53094

Middle Eastern (MID) AF: 0.274 AC: 1520 AN: 5542

European-Non Finnish (NFE) AF: 0.455 AC: 471807 AN: 1036426

Other (OTH) AF: 0.387 AC: 22260 AN: 57522

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

African (AFR) AF: 0.150 AC: 6217 AN: 41486

American (AMR) AF: 0.273 AC: 4179 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.402 AC: 1394 AN: 3468

East Asian (EAS) AF: 0.281 AC: 1448 AN: 5160

South Asian (SAS) AF: 0.262 AC: 1265 AN: 4820

European-Finnish (FIN) AF: 0.362 AC: 3815 AN: 10552

Middle Eastern (MID) AF: 0.301 AC: 88 AN: 292

European-Non Finnish (NFE) AF: 0.443 AC: 30103 AN: 67956

Other (OTH) AF: 0.328 AC: 691 AN: 2106

Alfa AF: 0.405 Hom.: 52567

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
PhyloP100		-0.14
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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