rs309371

Variant names:

• chr4-122743092-G-A
• rs309371
• NM_152618.3:c.1200G>A

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.1200G>A​(p.Val400Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0311 in 1,614,144 control chromosomes in the GnomAD database, including 3,323 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.090 (1610 hom., cov: 33)
  • Exomes 𝑓: 0.025 (1713 hom.)
• Consequence: BBS12 NM_152618.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -1.08
• Publications: 9 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=-0.91).
• BP6: Variant 4-122743092-G-A is Benign according to our data. Variant chr4-122743092-G-A is described in ClinVar as Benign. ClinVar VariationId is 262669.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.08 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.271 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.1200G>A	p.Val400Val	synonymous	Exon 2 of 2	NP_689831.2
	BBS12	NM_001178007.2		c.1200G>A	p.Val400Val	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.1200G>A	p.Val400Val	synonymous	Exon 2 of 2	ENSP00000319062.3	Q6ZW61
	BBS12	ENST00000542236.5	TSL:2	c.1200G>A	p.Val400Val	synonymous	Exon 3 of 3	ENSP00000438273.1	Q6ZW61

Frequencies

GnomAD3 genomes AF: 0.0903 AC: 13740 AN: 152190 Hom.: 1598 Cov.: 33

Gnomad AFR AF: 0.275

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0450

Gnomad ASJ AF: 0.0435

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00320

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0187

Gnomad OTH AF: 0.0827

GnomAD2 exomes AF: 0.0335 AC: 8420 AN: 251430 AF XY: 0.0279

Gnomad AFR exome AF: 0.279

Gnomad AMR exome AF: 0.0258

Gnomad ASJ exome AF: 0.0489

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00443

Gnomad NFE exome AF: 0.0189

Gnomad OTH exome AF: 0.0329

GnomAD4 exome AF: 0.0249 AC: 36363 AN: 1461836 Hom.: 1713 Cov.: 69 AF XY: 0.0232 AC XY: 16840 AN XY: 727222

African (AFR) AF: 0.281 AC: 9391 AN: 33478

American (AMR) AF: 0.0287 AC: 1283 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0494 AC: 1291 AN: 26134

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

South Asian (SAS) AF: 0.00181 AC: 156 AN: 86258

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

Middle Eastern (MID) AF: 0.0296 AC: 171 AN: 5768

European-Non Finnish (NFE) AF: 0.0193 AC: 21485 AN: 1111960

Other (OTH) AF: 0.0378 AC: 2283 AN: 60396

GnomAD4 genome AF: 0.0905 AC: 13780 AN: 152308 Hom.: 1610 Cov.: 33 AF XY: 0.0874 AC XY: 6510 AN XY: 74480

African (AFR) AF: 0.276 AC: 11445 AN: 41530

American (AMR) AF: 0.0448 AC: 686 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0435 AC: 151 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00103 AC: 5 AN: 4832

European-Finnish (FIN) AF: 0.00320 AC: 34 AN: 10624

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0187 AC: 1273 AN: 68036

Other (OTH) AF: 0.0818 AC: 173 AN: 2114

Alfa AF: 0.0453 Hom.: 885

Bravo AF: 0.104

Asia WGS AF: 0.0210 AC: 73 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.015
DANN	Benign	0.50
PhyloP100		-1.1
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: rs309371; hg19: chr4-123664247;