chr11-116763231-G-A

Variant names:

• chr11-116763231-G-A
• rs10488698
• NM_032725.4:c.358C>T

Variant summary

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

The NM_032725.4(BUD13):​c.358C>T​(p.Arg120Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0551 in 1,547,288 control chromosomes in the GnomAD database, including 2,639 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R120H) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.049 (265 hom., cov: 32)
  • Exomes 𝑓: 0.056 (2374 hom.)
• Consequence: BUD13 NM_032725.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.01
• Publications: 42 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 (MetaRNN=0.0017531514).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0964 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.358C>T	p.Arg120Cys	missense	Exon 4 of 10	NP_116114.1
	BUD13	NM_001159736.2		c.358C>T	p.Arg120Cys	missense	Exon 4 of 10	NP_001153208.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BUD13	ENST00000260210.5	TSL:1 MANE Select	c.358C>T	p.Arg120Cys	missense	Exon 4 of 10	ENSP00000260210.3
	BUD13	ENST00000375445.7	TSL:1	c.358C>T	p.Arg120Cys	missense	Exon 4 of 10	ENSP00000364594.3
	ENSG00000308823	ENST00000836679.1		n.434-2019G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0495 AC: 7532 AN: 152078 Hom.: 265 Cov.: 32

Gnomad AFR AF: 0.0128

Gnomad AMI AF: 0.0934

Gnomad AMR AF: 0.100

Gnomad ASJ AF: 0.0478

Gnomad EAS AF: 0.0681

Gnomad SAS AF: 0.0473

Gnomad FIN AF: 0.0587

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0568

Gnomad OTH AF: 0.0579

GnomAD2 exomes AF: 0.0641 AC: 12553 AN: 195762 AF XY: 0.0631

Gnomad AFR exome AF: 0.0115

Gnomad AMR exome AF: 0.123

Gnomad ASJ exome AF: 0.0391

Gnomad EAS exome AF: 0.0743

Gnomad FIN exome AF: 0.0598

Gnomad NFE exome AF: 0.0614

Gnomad OTH exome AF: 0.0658

GnomAD4 exome AF: 0.0557 AC: 77689 AN: 1395092 Hom.: 2374 Cov.: 34 AF XY: 0.0556 AC XY: 38154 AN XY: 686682

African (AFR) AF: 0.0109 AC: 343 AN: 31408

American (AMR) AF: 0.117 AC: 4017 AN: 34450

Ashkenazi Jewish (ASJ) AF: 0.0481 AC: 1033 AN: 21482

East Asian (EAS) AF: 0.0600 AC: 2344 AN: 39088

South Asian (SAS) AF: 0.0414 AC: 3117 AN: 75246

European-Finnish (FIN) AF: 0.0574 AC: 2920 AN: 50902

Middle Eastern (MID) AF: 0.0825 AC: 449 AN: 5440

European-Non Finnish (NFE) AF: 0.0558 AC: 60260 AN: 1079636

Other (OTH) AF: 0.0558 AC: 3206 AN: 57440

GnomAD4 genome AF: 0.0494 AC: 7524 AN: 152196 Hom.: 265 Cov.: 32 AF XY: 0.0508 AC XY: 3778 AN XY: 74392

African (AFR) AF: 0.0127 AC: 529 AN: 41520

American (AMR) AF: 0.101 AC: 1538 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0478 AC: 166 AN: 3470

East Asian (EAS) AF: 0.0679 AC: 351 AN: 5170

South Asian (SAS) AF: 0.0471 AC: 227 AN: 4818

European-Finnish (FIN) AF: 0.0587 AC: 623 AN: 10616

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0568 AC: 3864 AN: 67992

Other (OTH) AF: 0.0563 AC: 119 AN: 2112

Alfa AF: 0.0560 Hom.: 934

Bravo AF: 0.0525

TwinsUK AF: 0.0537 AC: 199

ALSPAC AF: 0.0545 AC: 210

ESP6500AA AF: 0.0114 AC: 50

ESP6500EA AF: 0.0541 AC: 465

ExAC AF: 0.0607 AC: 7347

Asia WGS AF: 0.0680 AC: 235 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.74	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	16
DANN	Benign	0.82
DEOGEN2	Benign	0.0085	T
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.044	N
LIST_S2	Benign	0.80	T
MetaRNN	Benign	0.0018	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PhyloP100		1.0
PrimateAI	Benign	0.21	T
PROVEAN	Uncertain	-3.7	D
REVEL	Benign	0.12
Sift	Benign	0.14	T
Sift4G	Uncertain	0.044	D
Polyphen		0.0020	B
Vest4		0.12
MPC		0.13
ClinPred		0.011	T
GERP RS		3.9
Varity_R		0.074
gMVP		0.079
Mutation Taster		=97/3	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs10488698; hg19: chr11-116633947; COSMIC: COSV52767043; COSMIC: COSV52767043;