rs309358

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_152618.3(BBS12):c.-124G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 152,466 control chromosomes in the GnomAD database, including 3,498 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 3494 hom., cov: 33)

Exomes 𝑓: 0.23 ( 4 hom. )

Consequence

BBS12
NM_152618.3 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.452

Publications

6 publications found

Variant links:

Genes affected

BBS12 (HGNC:26648): (Bardet-Biedl syndrome 12) The protein encoded by this gene is part of a complex that is involved in membrane trafficking. The encoded protein is a molecular chaperone that aids in protein folding upon ATP hydrolysis. This protein also plays a role in adipocyte differentiation. Defects in this gene are a cause of Bardet-Biedl syndrome type 12. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, May 2010]

BBS12 Gene-Disease associations (from GenCC):

Bardet-Biedl syndrome 12
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, G2P, Ambry Genetics, Myriad Women’s Health
ciliopathy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
Bardet-Biedl syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

BBS12 links:

ENSG00000293471 (HGNC:):

ENSG00000293471 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 4-122732771-G-A is Benign according to our data. Variant chr4-122732771-G-A is described in ClinVar as Benign. ClinVar VariationId is 347494.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.228 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152618.3. 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
	BBS12	NM_152618.3	MANE Select	c.-124G>A		5_prime_UTR	Exon 1 of 2	NP_689831.2
	BBS12	NM_001178007.2		c.-312G>A		5_prime_UTR	Exon 1 of 3	NP_001171478.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
BBS12	ENST00000314218.8	TSL:1 MANE Select	c.-124G>A	5_prime_UTR	Exon 1 of 2	ENSP00000319062.3
BBS12	ENST00000542236.5	TSL:2	c.-312G>A	5_prime_UTR	Exon 1 of 3	ENSP00000438273.1
BBS12	ENST00000433287.1	TSL:2	c.-312G>A	upstream_gene	N/A	ENSP00000398912.1

Frequencies

GnomAD3 genomes

AF:

0.205

AC:

31138

AN:

152134

Hom.:

3493

Cov.:

show subpopulations

Gnomad AFR

AF:

0.227

Gnomad AMI

AF:

0.167

Gnomad AMR

AF:

0.140

Gnomad ASJ

AF:

0.176

Gnomad EAS

AF:

0.00115

Gnomad SAS

AF:

0.127

Gnomad FIN

AF:

0.194

Gnomad MID

AF:

0.168

Gnomad NFE

AF:

0.231

Gnomad OTH

AF:

0.187

GnomAD4 exome

AF:

0.229

AC:

AN:

214

Hom.:

Cov.:

AF XY:

0.263

AC XY:

AN XY:

160

show subpopulations

African (AFR)

AF:

0.167

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.200

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.239

AC:

AN:

176

Other (OTH)

AF:

0.143

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

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:

0.205

AC:

31158

AN:

152252

Hom.:

3494

Cov.:

AF XY:

0.199

AC XY:

14784

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.227

AC:

9413

AN:

41542

American (AMR)

AF:

0.140

AC:

2144

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.176

AC:

611

AN:

3472

East Asian (EAS)

AF:

0.00116

AC:

AN:

5190

South Asian (SAS)

AF:

0.127

AC:

612

AN:

4822

European-Finnish (FIN)

AF:

0.194

AC:

2061

AN:

10604

Middle Eastern (MID)

AF:

0.173

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.231

AC:

15719

AN:

68000

Other (OTH)

AF:

0.184

AC:

389

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1284

2568

3853

5137

6421

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

330

660

990

1320

1650

<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:

0.224

Hom.:

1369

Bravo

AF:

0.201

Asia WGS

AF:

0.0740

AC:

256

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Bardet-Biedl syndrome 12

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

7.9

(source)

DANN

Benign

0.75

PhyloP100

0.45

PromoterAI

0.11

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over