rs17006077

Positions:

• chr4-122741943-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_152618.3(BBS12):​c.51A>G​(p.Gln17Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.012 in 1,613,914 control chromosomes in the GnomAD database, including 1,785 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.062 (997 hom., cov: 33)
  • Exomes 𝑓: 0.0068 (788 hom.)
• Consequence: BBS12 NM_152618.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.458

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 4-122741943-A-G is Benign according to our data. Variant chr4-122741943-A-G is described in ClinVar as [Benign]. Clinvar id is 262675.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-122741943-A-G is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=0.458 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BBS12	NM_152618.3	c.51A>G	p.Gln17Gln	synonymous_variant	2/2	ENST00000314218.8	NP_689831.2
BBS12	NM_001178007.2	c.51A>G	p.Gln17Gln	synonymous_variant	3/3		NP_001171478.1
BBS12	XM_011531680.3	c.51A>G	p.Gln17Gln	synonymous_variant	2/2		XP_011529982.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BBS12	ENST00000314218.8	c.51A>G	p.Gln17Gln	synonymous_variant	2/2	1	NM_152618.3	ENSP00000319062.3
BBS12	ENST00000542236.5	c.51A>G	p.Gln17Gln	synonymous_variant	3/3	2		ENSP00000438273.1
BBS12	ENST00000433287.1	c.51A>G	p.Gln17Gln	synonymous_variant	3/3	2		ENSP00000398912.1

Frequencies

GnomAD3 genomes AF: 0.0619 AC: 9422 AN: 152144 Hom.: 992 Cov.: 33

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0289

Gnomad ASJ AF: 0.0159

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.00112

Gnomad OTH AF: 0.0492

GnomAD3 exomes AF: 0.0172 AC: 4331 AN: 251198 Hom.: 385 AF XY: 0.0123 AC XY: 1673 AN XY: 135768

Gnomad AFR exome AF: 0.217

Gnomad AMR exome AF: 0.0127

Gnomad ASJ exome AF: 0.0142

Gnomad EAS exome AF: 0.000979

Gnomad SAS exome AF: 0.000393

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00113

Gnomad OTH exome AF: 0.00963

GnomAD4 exome AF: 0.00682 AC: 9970 AN: 1461652 Hom.: 788 Cov.: 31 AF XY: 0.00584 AC XY: 4245 AN XY: 727090

Gnomad4 AFR exome AF: 0.215

Gnomad4 AMR exome AF: 0.0142

Gnomad4 ASJ exome AF: 0.0141

Gnomad4 EAS exome AF: 0.000403

Gnomad4 SAS exome AF: 0.000580

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000687

Gnomad4 OTH exome AF: 0.0146

GnomAD4 genome AF: 0.0621 AC: 9451 AN: 152262 Hom.: 997 Cov.: 33 AF XY: 0.0610 AC XY: 4544 AN XY: 74466

Gnomad4 AFR AF: 0.211

Gnomad4 AMR AF: 0.0288

Gnomad4 ASJ AF: 0.0159

Gnomad4 EAS AF: 0.000771

Gnomad4 SAS AF: 0.000828

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00112

Gnomad4 OTH AF: 0.0487

Alfa AF: 0.0157 Hom.: 299

Bravo AF: 0.0710

Asia WGS AF: 0.0160 AC: 55 AN: 3478

EpiCase AF: 0.000872

EpiControl AF: 0.00178

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 04, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Bardet-Biedl syndrome 12 Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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. -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Bardet-Biedl syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	2.7
DANN	Benign	0.42

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

LitVar

Other links and lift over

dbSNP: rs17006077; hg19: chr4-123663098;