rs17006092

Variant names:

• chr4-122743101-G-A
• rs17006092
• NM_152618.3:c.1209G>A

Your query was ambiguous. Multiple possible variants found:

• chr4-122743101-G-A
• chr4-122743101-G-C

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.1209G>A​(p.Val403Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0196 in 1,614,194 control chromosomes in the GnomAD database, including 551 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. V403V) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.033 (170 hom., cov: 33)
  • Exomes 𝑓: 0.018 (381 hom.)
• Consequence: BBS12 NM_152618.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -0.831
• 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=-0.87).
• BP6: Variant 4-122743101-G-A is Benign according to our data. Variant chr4-122743101-G-A is described in ClinVar as Benign. ClinVar VariationId is 262670.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.831 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0769 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.1209G>A	p.Val403Val	synonymous	Exon 2 of 2	NP_689831.2
	BBS12	NM_001178007.2		c.1209G>A	p.Val403Val	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.1209G>A	p.Val403Val	synonymous	Exon 2 of 2	ENSP00000319062.3
	BBS12	ENST00000542236.5	TSL:2	c.1209G>A	p.Val403Val	synonymous	Exon 3 of 3	ENSP00000438273.1

Frequencies

GnomAD3 genomes AF: 0.0331 AC: 5043 AN: 152214 Hom.: 167 Cov.: 33

Gnomad AFR AF: 0.0787

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0245

Gnomad ASJ AF: 0.0277

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00320

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0175

Gnomad OTH AF: 0.0378

GnomAD2 exomes AF: 0.0174 AC: 4380 AN: 251454 AF XY: 0.0159

Gnomad AFR exome AF: 0.0815

Gnomad AMR exome AF: 0.0146

Gnomad ASJ exome AF: 0.0290

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00443

Gnomad NFE exome AF: 0.0175

Gnomad OTH exome AF: 0.0215

GnomAD4 exome AF: 0.0182 AC: 26630 AN: 1461862 Hom.: 381 Cov.: 68 AF XY: 0.0173 AC XY: 12608 AN XY: 727230

African (AFR) AF: 0.0771 AC: 2581 AN: 33480

American (AMR) AF: 0.0158 AC: 708 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0298 AC: 778 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00115 AC: 99 AN: 86258

European-Finnish (FIN) AF: 0.00565 AC: 302 AN: 53420

Middle Eastern (MID) AF: 0.0144 AC: 83 AN: 5768

European-Non Finnish (NFE) AF: 0.0186 AC: 20713 AN: 1111982

Other (OTH) AF: 0.0226 AC: 1365 AN: 60396

GnomAD4 genome AF: 0.0333 AC: 5067 AN: 152332 Hom.: 170 Cov.: 33 AF XY: 0.0322 AC XY: 2398 AN XY: 74506

African (AFR) AF: 0.0791 AC: 3288 AN: 41560

American (AMR) AF: 0.0243 AC: 372 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0277 AC: 96 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00320 AC: 34 AN: 10622

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0175 AC: 1193 AN: 68034

Other (OTH) AF: 0.0374 AC: 79 AN: 2112

Alfa AF: 0.0206 Hom.: 110

Bravo AF: 0.0370

Asia WGS AF: 0.00982 AC: 34 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.077
DANN	Benign	0.52
PhyloP100		-0.83
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: rs17006092; hg19: chr4-123664256;