Variant 14-74046117-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_025057.3(BBOF1):c.634C>T(p.His212Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000292 in 1,607,510 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

BBOF1
NM_025057.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.42

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 made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1959981).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BBOF1	NM_025057.3 linkuse as main transcript	c.634C>T	p.His212Tyr	missense_variant	6/12	ENST00000394009.5	NP_079333.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BBOF1	ENST00000394009.5 linkuse as main transcript	c.634C>T	p.His212Tyr	missense_variant	6/12	2	NM_025057.3	ENSP00000377577	P1

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000378

AC:

AN:

238122

Hom.:

AF XY:

0.0000465

AC XY:

AN XY:

128982

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000837

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000289

AC:

AN:

1455228

Hom.:

Cov.:

AF XY:

0.0000277

AC XY:

AN XY:

723180

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000370

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152282

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000965

Hom.:

Bravo

AF:

0.0000416

ExAC

AF:

0.0000581

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 06, 2023

The c.634C>T (p.H212Y) alteration is located in exon 6 (coding exon 6) of the BBOF1 gene. This alteration results from a C to T substitution at nucleotide position 634, causing the histidine (H) at amino acid position 212 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.48

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0032

.;T

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.71

T;T

M_CAP

Benign

0.0057

MetaRNN

Benign

0.20

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

.;M

MutationTaster

Benign

0.96

D;D

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-1.6

N;N

REVEL

Benign

0.067

Sift

Benign

0.69

T;T

Sift4G

Uncertain

0.047

D;T

Polyphen

0.78

.;P

Vest4

0.49

MVP

0.51

MPC

0.32

ClinPred

0.25

GERP RS

5.9

Varity_R

0.17

gMVP

0.20

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over