rs13102440

Variant names:

• chr4-122743764-A-G
• rs13102440
• NM_152618.3:c.1872A>G

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.1872A>G​(p.Gln624Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 1,613,900 control chromosomes in the GnomAD database, including 37,011 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2420 hom., cov: 33)
  • Exomes 𝑓: 0.21 (34591 hom.)
• Consequence: BBS12 NM_152618.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: 1.82
• Publications: 19 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=-0.84).
• BP6: Variant 4-122743764-A-G is Benign according to our data. Variant chr4-122743764-A-G is described in ClinVar as Benign. ClinVar VariationId is 166730.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.82 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.227 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.1872A>G	p.Gln624Gln	synonymous	Exon 2 of 2	NP_689831.2
	BBS12	NM_001178007.2		c.1872A>G	p.Gln624Gln	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.1872A>G	p.Gln624Gln	synonymous	Exon 2 of 2	ENSP00000319062.3
	BBS12	ENST00000542236.5	TSL:2	c.1872A>G	p.Gln624Gln	synonymous	Exon 3 of 3	ENSP00000438273.1

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23789 AN: 152134 Hom.: 2420 Cov.: 33

Gnomad AFR AF: 0.0596

Gnomad AMI AF: 0.167

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.230

Gnomad OTH AF: 0.151

GnomAD2 exomes AF: 0.165 AC: 41310 AN: 251120 AF XY: 0.170

Gnomad AFR exome AF: 0.0569

Gnomad AMR exome AF: 0.0822

Gnomad ASJ exome AF: 0.166

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.200

Gnomad NFE exome AF: 0.231

Gnomad OTH exome AF: 0.181

GnomAD4 exome AF: 0.209 AC: 305500 AN: 1461648 Hom.: 34591 Cov.: 34 AF XY: 0.208 AC XY: 151460 AN XY: 727122

African (AFR) AF: 0.0567 AC: 1898 AN: 33480

American (AMR) AF: 0.0864 AC: 3863 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 4336 AN: 26132

East Asian (EAS) AF: 0.000453 AC: 18 AN: 39700

South Asian (SAS) AF: 0.137 AC: 11815 AN: 86234

European-Finnish (FIN) AF: 0.205 AC: 10932 AN: 53376

Middle Eastern (MID) AF: 0.160 AC: 923 AN: 5768

European-Non Finnish (NFE) AF: 0.234 AC: 260659 AN: 1111852

Other (OTH) AF: 0.183 AC: 11056 AN: 60390

GnomAD4 genome AF: 0.156 AC: 23790 AN: 152252 Hom.: 2420 Cov.: 33 AF XY: 0.152 AC XY: 11303 AN XY: 74448

African (AFR) AF: 0.0596 AC: 2476 AN: 41560

American (AMR) AF: 0.123 AC: 1884 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 575 AN: 3472

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

South Asian (SAS) AF: 0.126 AC: 609 AN: 4822

European-Finnish (FIN) AF: 0.195 AC: 2066 AN: 10588

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.230 AC: 15661 AN: 67992

Other (OTH) AF: 0.148 AC: 314 AN: 2116

Alfa AF: 0.199 Hom.: 11121

Bravo AF: 0.145

Asia WGS AF: 0.0640 AC: 224 AN: 3478

EpiCase AF: 0.221

EpiControl AF: 0.220

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.3
DANN	Benign	0.43
PhyloP100		1.8
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: rs13102440; hg19: chr4-123664919; COSMIC: COSV58563424; COSMIC: COSV58563424;