rs202205304

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_024649.5(BBS1):c.1535G>A(p.Arg512His) variant causes a missense change. The variant allele was found at a frequency of 0.0000415 in 1,614,186 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R512C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000038 ( 0 hom. )

Consequence

BBS1
NM_024649.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:9

Conservation

PhyloP100: 6.45

Publications

2 publications found

Variant links:

Genes affected

BBS1 (HGNC:966): (Bardet-Biedl syndrome 1) Mutations in this gene have been observed in patients with the major form (type 1) of Bardet-Biedl syndrome. The encoded protein may play a role in eye, limb, cardiac and reproductive system development. [provided by RefSeq, Jul 2008]

BBS1 links:

ENSG00000256349 (HGNC:):

ENSG00000256349 links:

ZDHHC24 (HGNC:27387): (zinc finger DHHC-type containing 24) Predicted to enable protein-cysteine S-palmitoyltransferase activity. Predicted to be involved in peptidyl-L-cysteine S-palmitoylation and protein targeting to membrane. Predicted to be integral component of membrane. Predicted to be active in Golgi apparatus and endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ZDHHC24 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.804

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024649.5. 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
	BBS1	NM_024649.5	MANE Select	c.1535G>A	p.Arg512His	missense	Exon 15 of 17	NP_078925.3
	ZDHHC24	NM_001348571.2		c.560-1467C>T		intron	N/A	NP_001335500.1	E9PLR9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BBS1	ENST00000318312.12	TSL:1 MANE Select	c.1535G>A	p.Arg512His	missense	Exon 15 of 17	ENSP00000317469.7	Q8NFJ9-1
ENSG00000256349	ENST00000419755.3	TSL:2	c.1646G>A	p.Arg549His	missense	Exon 15 of 17	ENSP00000398526.3
BBS1	ENST00000393994.4	TSL:1	c.1148G>A	p.Arg383His	missense	Exon 12 of 13	ENSP00000377563.2	Q8NFJ9-3

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000636

AC:

AN:

251494

AF XY:

0.0000809

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000967

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000383

AC:

AN:

1461882

Hom.:

Cov.:

AF XY:

0.0000358

AC XY:

AN XY:

727244

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.0000447

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000580

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000423

AC:

AN:

1112006

Other (OTH)

AF:

0.0000166

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000722

AC:

AN:

152304

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.0000722

AC:

AN:

41568

American (AMR)

AF:

0.0000653

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000882

AC:

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

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:

0.0000784

Hom.:

Bravo

AF:

0.0000529

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000906

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Bardet-Biedl syndrome 1 (5)

not specified (2)

Bardet-Biedl syndrome (1)

BBS1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Pathogenic

0.27

BayesDel_noAF

Pathogenic

0.36

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.59

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.93

M_CAP

Pathogenic

0.29

MetaRNN

Pathogenic

0.80

MetaSVM

Pathogenic

0.99

MutationAssessor

Uncertain

2.5

PhyloP100

6.4

PrimateAI

Benign

0.44

PROVEAN

Benign

-2.0

REVEL

Pathogenic

0.69

Sift

Benign

0.031

Sift4G

Benign

0.10

Polyphen

1.0

Vest4

0.83

MVP

0.97

MPC

0.73

ClinPred

0.50

GERP RS

4.6

Varity_R

0.12

gMVP

0.59

Mutation Taster

=3/97

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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