rs309368

Variant names:

• chr4-122741842-A-T
• rs309368
• NM_152618.3:c.-10-41A>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_152618.3(BBS12):​c.-10-41A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 1,517,818 control chromosomes in the GnomAD database, including 36,947 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3481 hom., cov: 33)
  • Exomes 𝑓: 0.21 (33466 hom.)
• Consequence: BBS12 NM_152618.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.230
• Publications: 4 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 4-122741842-A-T is Benign according to our data. Variant chr4-122741842-A-T is described in ClinVar as Benign. ClinVar VariationId is 1174029.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.228 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.-10-41A>T		intron	N/A	NP_689831.2
	BBS12	NM_001178007.2		c.-10-41A>T		intron	N/A	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.-10-41A>T		intron	N/A	ENSP00000319062.3	Q6ZW61
	BBS12	ENST00000542236.5	TSL:2	c.-10-41A>T		intron	N/A	ENSP00000438273.1	Q6ZW61
	BBS12	ENST00000433287.1	TSL:2	c.-10-41A>T		intron	N/A	ENSP00000398912.1	C9J8H7

Frequencies

GnomAD3 genomes AF: 0.205 AC: 31106 AN: 152084 Hom.: 3480 Cov.: 33

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.167

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.186

GnomAD2 exomes AF: 0.176 AC: 40682 AN: 230680 AF XY: 0.179

Gnomad AFR exome AF: 0.225

Gnomad AMR exome AF: 0.0901

Gnomad ASJ exome AF: 0.180

Gnomad EAS exome AF: 0.000121

Gnomad FIN exome AF: 0.200

Gnomad NFE exome AF: 0.232

Gnomad OTH exome AF: 0.188

GnomAD4 exome AF: 0.214 AC: 292154 AN: 1365616 Hom.: 33466 Cov.: 22 AF XY: 0.213 AC XY: 145487 AN XY: 683918

African (AFR) AF: 0.229 AC: 6969 AN: 30462

American (AMR) AF: 0.0958 AC: 4193 AN: 43776

Ashkenazi Jewish (ASJ) AF: 0.181 AC: 4622 AN: 25482

East Asian (EAS) AF: 0.000396 AC: 15 AN: 37904

South Asian (SAS) AF: 0.138 AC: 11360 AN: 82256

European-Finnish (FIN) AF: 0.205 AC: 10818 AN: 52776

Middle Eastern (MID) AF: 0.167 AC: 933 AN: 5596

European-Non Finnish (NFE) AF: 0.235 AC: 242069 AN: 1030228

Other (OTH) AF: 0.196 AC: 11175 AN: 57136

GnomAD4 genome AF: 0.205 AC: 31126 AN: 152202 Hom.: 3481 Cov.: 33 AF XY: 0.198 AC XY: 14765 AN XY: 74412

African (AFR) AF: 0.226 AC: 9400 AN: 41524

American (AMR) AF: 0.140 AC: 2146 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.176 AC: 609 AN: 3470

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5190

South Asian (SAS) AF: 0.127 AC: 613 AN: 4830

European-Finnish (FIN) AF: 0.195 AC: 2060 AN: 10576

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.231 AC: 15701 AN: 67998

Other (OTH) AF: 0.184 AC: 388 AN: 2114

Alfa AF: 0.213 Hom.: 668

Bravo AF: 0.201

Asia WGS AF: 0.0730 AC: 254 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.7
DANN	Benign	0.76
PhyloP100		0.23
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: rs309368; hg19: chr4-123662997;