rs17006077

Variant names:

• chr4-122741943-A-G
• rs17006077
• NM_152618.3:c.51A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 262675.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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.

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.51A>G	p.Gln17Gln	synonymous	Exon 2 of 2	NP_689831.2
	BBS12	NM_001178007.2		c.51A>G	p.Gln17Gln	synonymous	Exon 3 of 3	NP_001171478.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BBS12	ENST00000314218.8	TSL:1 MANE Select	c.51A>G	p.Gln17Gln	synonymous	Exon 2 of 2	ENSP00000319062.3
	BBS12	ENST00000542236.5	TSL:2	c.51A>G	p.Gln17Gln	synonymous	Exon 3 of 3	ENSP00000438273.1
	BBS12	ENST00000433287.1	TSL:2	c.51A>G	p.Gln17Gln	synonymous	Exon 3 of 3	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

GnomAD2 exomes AF: 0.0172 AC: 4331 AN: 251198 AF XY: 0.0123

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 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

African (AFR) AF: 0.215 AC: 7196 AN: 33460

American (AMR) AF: 0.0142 AC: 634 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.0141 AC: 369 AN: 26128

East Asian (EAS) AF: 0.000403 AC: 16 AN: 39680

South Asian (SAS) AF: 0.000580 AC: 50 AN: 86214

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.0104 AC: 60 AN: 5768

European-Non Finnish (NFE) AF: 0.000687 AC: 764 AN: 1111908

Other (OTH) AF: 0.0146 AC: 881 AN: 60384

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

African (AFR) AF: 0.211 AC: 8759 AN: 41506

American (AMR) AF: 0.0288 AC: 441 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0159 AC: 55 AN: 3470

East Asian (EAS) AF: 0.000771 AC: 4 AN: 5186

South Asian (SAS) AF: 0.000828 AC: 4 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.00112 AC: 76 AN: 68026

Other (OTH) AF: 0.0487 AC: 103 AN: 2116

Alfa AF: 0.0224 Hom.: 547

Bravo AF: 0.0710

Asia WGS AF: 0.0160 AC: 55 AN: 3478

EpiCase AF: 0.000872

EpiControl AF: 0.00178

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Bardet-Biedl syndrome 12 (2)
-	-	2	not provided (2)
-	-	1	Bardet-Biedl syndrome (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	2.7
DANN	Benign	0.42
PhyloP100		0.46
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17006077; hg19: chr4-123663098;