rs2292493

Variant names:

• chr4-122743290-C-T
• rs2292493
• NM_152618.3:c.1398C>T

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.1398C>T​(p.Gly466Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 1,613,970 control chromosomes in the GnomAD database, including 26,699 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (2915 hom., cov: 33)
  • Exomes 𝑓: 0.13 (23784 hom.)
• Consequence: BBS12 NM_152618.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -0.621
• Publications: 20 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, Myriad Women’s Health, G2P, Ambry Genetics
• BBS12-related 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=-0.69).
• BP6: Variant 4-122743290-C-T is Benign according to our data. Variant chr4-122743290-C-T is described in ClinVar as Benign. ClinVar VariationId is 262672.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.621 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.627 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BBS12	NM_152618.3	MANE Select	c.1398C>T	p.Gly466Gly	synonymous	Exon 2 of 2	NP_689831.2
	BBS12	NM_001178007.2		c.1398C>T	p.Gly466Gly	synonymous	Exon 3 of 3	NP_001171478.1	Q6ZW61

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BBS12	ENST00000314218.8	TSL:1 MANE Select	c.1398C>T	p.Gly466Gly	synonymous	Exon 2 of 2	ENSP00000319062.3	Q6ZW61
	BBS12	ENST00000542236.5	TSL:2	c.1398C>T	p.Gly466Gly	synonymous	Exon 3 of 3	ENSP00000438273.1	Q6ZW61

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23139 AN: 151998 Hom.: 2907 Cov.: 33

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.644

Gnomad SAS AF: 0.347

Gnomad FIN AF: 0.0771

Gnomad MID AF: 0.255

Gnomad NFE AF: 0.0898

Gnomad OTH AF: 0.164

GnomAD2 exomes AF: 0.209 AC: 52549 AN: 251410 AF XY: 0.207

Gnomad AFR exome AF: 0.140

Gnomad AMR exome AF: 0.379

Gnomad ASJ exome AF: 0.150

Gnomad EAS exome AF: 0.662

Gnomad FIN exome AF: 0.0803

Gnomad NFE exome AF: 0.0892

Gnomad OTH exome AF: 0.172

GnomAD4 exome AF: 0.129 AC: 188509 AN: 1461854 Hom.: 23784 Cov.: 62 AF XY: 0.135 AC XY: 97894 AN XY: 727220

African (AFR) AF: 0.141 AC: 4727 AN: 33478

American (AMR) AF: 0.370 AC: 16541 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 3852 AN: 26136

East Asian (EAS) AF: 0.671 AC: 26622 AN: 39700

South Asian (SAS) AF: 0.338 AC: 29162 AN: 86254

European-Finnish (FIN) AF: 0.0811 AC: 4331 AN: 53416

Middle Eastern (MID) AF: 0.216 AC: 1244 AN: 5768

European-Non Finnish (NFE) AF: 0.0826 AC: 91885 AN: 1111986

Other (OTH) AF: 0.168 AC: 10145 AN: 60396

GnomAD4 genome AF: 0.152 AC: 23172 AN: 152116 Hom.: 2915 Cov.: 33 AF XY: 0.161 AC XY: 11958 AN XY: 74364

African (AFR) AF: 0.139 AC: 5779 AN: 41454

American (AMR) AF: 0.283 AC: 4334 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 516 AN: 3470

East Asian (EAS) AF: 0.645 AC: 3335 AN: 5170

South Asian (SAS) AF: 0.346 AC: 1670 AN: 4822

European-Finnish (FIN) AF: 0.0771 AC: 817 AN: 10592

Middle Eastern (MID) AF: 0.257 AC: 75 AN: 292

European-Non Finnish (NFE) AF: 0.0898 AC: 6106 AN: 68004

Other (OTH) AF: 0.168 AC: 355 AN: 2108

Alfa AF: 0.132 Hom.: 3326

Bravo AF: 0.170

Asia WGS AF: 0.509 AC: 1766 AN: 3478

EpiCase AF: 0.0997

EpiControl AF: 0.0984

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Bardet-Biedl syndrome 12 (3)
-	-	3	not specified (3)
-	-	2	not provided (2)
-	-	1	Bardet-Biedl syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	7.1
DANN	Benign	0.38
PhyloP100		-0.62
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: rs2292493; hg19: chr4-123664445; COSMIC: COSV58561221; COSMIC: COSV58561221;