rs2293489

Positions:

• chr7-73692949-C-T

Variant summary

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

The NM_017528.5(BUD23):​c.510+303C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.303 in 538,978 control chromosomes in the GnomAD database, including 27,383 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 0.26 (6393 hom., cov: 32)
  • Exomes 𝑓: 0.32 (20990 hom.)
• Consequence: BUD23 NM_017528.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06

Genes affected

BUD23 (HGNC:16405): (BUD23 rRNA methyltransferase and ribosome maturation factor) This gene encodes a protein containing a nuclear localization signal and an S-adenosyl-L-methionine binding motif typical of methyltransferases, suggesting that the encoded protein may act on DNA methylation. This gene is deleted in Williams syndrome, a multisystem developmental disorder caused by the deletion of contiguous genes at 7q11.23. Alternatively spliced transcript variants have been found. [provided by RefSeq, Feb 2011]

BUD23 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.341 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BUD23	NM_017528.5	c.510+303C>T		intron_variant		ENST00000265758.7	NP_059998.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BUD23	ENST00000265758.7	c.510+303C>T		intron_variant		1	NM_017528.5	ENSP00000265758.3

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39958 AN: 151892 Hom.: 6397 Cov.: 32

Gnomad AFR AF: 0.0774

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.242

Gnomad EAS AF: 0.153

Gnomad SAS AF: 0.350

Gnomad FIN AF: 0.422

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.345

Gnomad OTH AF: 0.267

GnomAD4 exome AF: 0.319 AC: 123561 AN: 386968 Hom.: 20990 Cov.: 0 AF XY: 0.321 AC XY: 64485 AN XY: 201124

Gnomad4 AFR exome AF: 0.0752

Gnomad4 AMR exome AF: 0.316

Gnomad4 ASJ exome AF: 0.256

Gnomad4 EAS exome AF: 0.186

Gnomad4 SAS exome AF: 0.339

Gnomad4 FIN exome AF: 0.418

Gnomad4 NFE exome AF: 0.341

Gnomad4 OTH exome AF: 0.295

GnomAD4 genome AF: 0.263 AC: 39956 AN: 152010 Hom.: 6393 Cov.: 32 AF XY: 0.267 AC XY: 19844 AN XY: 74302

Gnomad4 AFR AF: 0.0772

Gnomad4 AMR AF: 0.307

Gnomad4 ASJ AF: 0.242

Gnomad4 EAS AF: 0.152

Gnomad4 SAS AF: 0.349

Gnomad4 FIN AF: 0.422

Gnomad4 NFE AF: 0.345

Gnomad4 OTH AF: 0.271

Alfa AF: 0.320 Hom.: 8756

Bravo AF: 0.243

Asia WGS AF: 0.264 AC: 920 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.30
DANN	Benign	0.82

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

Publications

LitVar

Other links and lift over

dbSNP: rs2293489; hg19: chr7-73107279;