Genetic Variant BBOF1:p.Lys274Asn (chr14-74049731-G-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_025057.3(BBOF1):c.822G>T(p.Lys274Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000992 in 1,610,606 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00051 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0010 ( 1 hom. )

Consequence

BBOF1
NM_025057.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.12

Publications

3 publications found

Variant links:

Genes affected

BBOF1 (HGNC:19855): (basal body orientation factor 1) Predicted to be involved in motile cilium assembly. Predicted to be located in ciliary basal body. [provided by Alliance of Genome Resources, Apr 2022]

BBOF1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.052048713).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025057.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BBOF1	NM_025057.3	MANE Select	c.822G>T	p.Lys274Asn	missense	Exon 8 of 12	NP_079333.2	Q8ND07

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BBOF1	ENST00000394009.5	TSL:2 MANE Select	c.822G>T	p.Lys274Asn	missense	Exon 8 of 12	ENSP00000377577.3	Q8ND07
BBOF1	ENST00000901146.1		c.678G>T	p.Lys226Asn	missense	Exon 7 of 11	ENSP00000571205.1
BBOF1	ENST00000901145.1		c.647+3601G>T		intron	N/A	ENSP00000571204.1

Frequencies

GnomAD3 genomes

AF:

0.000519

AC:

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000754

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000838

Gnomad OTH

AF:

0.00143

GnomAD2 exomes

AF:

0.000523

AC:

129

AN:

246746

AF XY:

0.000544

show subpopulations

Gnomad AFR exome

AF:

0.0000650

Gnomad AMR exome

AF:

0.0000299

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000278

Gnomad NFE exome

AF:

0.00107

Gnomad OTH exome

AF:

0.000167

GnomAD4 exome

AF:

0.00104

AC:

1519

AN:

1458350

Hom.:

Cov.:

AF XY:

0.000997

AC XY:

723

AN XY:

725480

show subpopulations

African (AFR)

AF:

0.0000904

AC:

AN:

33180

American (AMR)

AF:

0.0000689

AC:

AN:

43526

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25962

East Asian (EAS)

AF:

0.00

AC:

AN:

39660

South Asian (SAS)

AF:

0.00

AC:

AN:

85950

European-Finnish (FIN)

AF:

0.000450

AC:

AN:

53380

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5744

European-Non Finnish (NFE)

AF:

0.00130

AC:

1444

AN:

1110744

Other (OTH)

AF:

0.000731

AC:

AN:

60204

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

148

221

295

369

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

180

240

300

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000512

AC:

AN:

152256

Hom.:

Cov.:

AF XY:

0.000470

AC XY:

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.000217

AC:

AN:

41562

American (AMR)

AF:

0.000131

AC:

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.000754

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000823

AC:

AN:

68028

Other (OTH)

AF:

0.00142

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000767

Hom.:

Bravo

AF:

0.000457

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000943

AC:

ExAC

AF:

0.000718

AC:

EpiCase

AF:

0.00147

EpiControl

AF:

0.000653

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.52

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.053

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.70

M_CAP

Benign

0.0094

MetaRNN

Benign

0.052

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

PhyloP100

2.1

PrimateAI

Uncertain

0.54

PROVEAN

Uncertain

-2.8

REVEL

Benign

0.14

Sift

Benign

0.12

Sift4G

Benign

0.14

Polyphen

1.0

Vest4

0.37

MutPred

0.32

Loss of ubiquitination at K274 (P = 0.0107)

MVP

0.61

MPC

0.46

ClinPred

0.11

GERP RS

4.9

Varity_R

0.29

gMVP

0.38

Mutation Taster

=83/17

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over