4-122741842-A-T

Variant summary

Our verdict is Benign. Variant got -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:2
• Conservation: PhyloP100: 0.230

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BBS12	NM_152618.3	c.-10-41A>T		intron_variant		ENST00000314218.8
BBS12	NM_001178007.2	c.-10-41A>T		intron_variant
BBS12	XM_011531680.3	c.-10-41A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BBS12	ENST00000314218.8	c.-10-41A>T		intron_variant		1	NM_152618.3	P1
BBS12	ENST00000433287.1	c.-10-41A>T		intron_variant		2
BBS12	ENST00000542236.5	c.-10-41A>T		intron_variant		2		P1

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

GnomAD3 exomes AF: 0.176 AC: 40682 AN: 230680 Hom.: 4190 AF XY: 0.179 AC XY: 22450 AN XY: 125570

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 SAS exome AF: 0.137

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

Gnomad4 AFR exome AF: 0.229

Gnomad4 AMR exome AF: 0.0958

Gnomad4 ASJ exome AF: 0.181

Gnomad4 EAS exome AF: 0.000396

Gnomad4 SAS exome AF: 0.138

Gnomad4 FIN exome AF: 0.205

Gnomad4 NFE exome AF: 0.235

Gnomad4 OTH exome AF: 0.196

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

Gnomad4 AFR AF: 0.226

Gnomad4 AMR AF: 0.140

Gnomad4 ASJ AF: 0.176

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.127

Gnomad4 FIN AF: 0.195

Gnomad4 NFE AF: 0.231

Gnomad4 OTH AF: 0.184

Alfa AF: 0.213 Hom.: 668

Bravo AF: 0.201

Asia WGS AF: 0.0730 AC: 254 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Bardet-Biedl syndrome 12 Benign:1

Benign, criteria provided, single submitter

clinical testing

Pars Genome Lab

Jun 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	4.7
Dann	Benign	0.76

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

Publications

LitVar

Other links and lift over

dbSNP: rs309368; hg19: chr4-123662997;