rs80334351

chr15-72716867-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_033028.5(BBS4):c.405+17C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0292 in 1,570,000 control chromosomes in the GnomAD database, including 1,090 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.026 (104 hom., cov: 32)
  • Exomes 𝑓: 0.030 (986 hom.)
• Consequence: BBS4 NM_033028.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.171

Genes affected

BBS4 (HGNC:969): (Bardet-Biedl syndrome 4) This gene is a member of the Bardet-Biedl syndrome (BBS) gene family. Bardet-Biedl syndrome is an autosomal recessive disorder characterized by severe pigmentary retinopathy, obesity, polydactyly, renal malformation and cognitive disability. The proteins encoded by BBS gene family members are structurally diverse. The similar phenotypes exhibited by mutations in BBS gene family members are likely due to the protein's shared roles in cilia formation and function. Many BBS proteins localize to the basal bodies, ciliary axonemes, and pericentriolar regions of cells. BBS proteins may also be involved in intracellular trafficking via microtubule-related transport. The protein encoded by this gene has sequence similarity to O-linked N-acetylglucosamine (O-GlcNAc) transferases in plants and archaebacteria and in human forms a multi-protein "BBSome" complex with seven other BBS proteins. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 15-72716867-C-T is Benign according to our data. Variant chr15-72716867-C-T is described in ClinVar as [Benign]. Clinvar id is 262139.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-72716867-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0697 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BBS4	NM_033028.5	c.405+17C>T		intron_variant		ENST00000268057.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BBS4	ENST00000268057.9	c.405+17C>T		intron_variant		1	NM_033028.5	P1

Frequencies

GnomAD3 genomes AF: 0.0257 AC: 3909 AN: 152188 Hom.: 104 Cov.: 32

Gnomad AFR AF: 0.00511

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.0733

Gnomad ASJ AF: 0.0323

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0315

Gnomad FIN AF: 0.0340

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0272

Gnomad OTH AF: 0.0287

GnomAD3 exomes AF: 0.0437 AC: 10459 AN: 239186 Hom.: 487 AF XY: 0.0406 AC XY: 5246 AN XY: 129128

Gnomad AFR exome AF: 0.00568

Gnomad AMR exome AF: 0.147

Gnomad ASJ exome AF: 0.0295

Gnomad EAS exome AF: 0.00121

Gnomad SAS exome AF: 0.0387

Gnomad FIN exome AF: 0.0360

Gnomad NFE exome AF: 0.0282

Gnomad OTH exome AF: 0.0425

GnomAD4 exome AF: 0.0296 AC: 41897 AN: 1417694 Hom.: 986 Cov.: 25 AF XY: 0.0295 AC XY: 20874 AN XY: 706524

Gnomad4 AFR exome AF: 0.00524

Gnomad4 AMR exome AF: 0.135

Gnomad4 ASJ exome AF: 0.0318

Gnomad4 EAS exome AF: 0.000786

Gnomad4 SAS exome AF: 0.0398

Gnomad4 FIN exome AF: 0.0367

Gnomad4 NFE exome AF: 0.0260

Gnomad4 OTH exome AF: 0.0264

GnomAD4 genome AF: 0.0256 AC: 3906 AN: 152306 Hom.: 104 Cov.: 32 AF XY: 0.0271 AC XY: 2020 AN XY: 74460

Gnomad4 AFR AF: 0.00510

Gnomad4 AMR AF: 0.0733

Gnomad4 ASJ AF: 0.0323

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0315

Gnomad4 FIN AF: 0.0340

Gnomad4 NFE AF: 0.0272

Gnomad4 OTH AF: 0.0284

Alfa AF: 0.0280 Hom.: 12

Bravo AF: 0.0292

Asia WGS AF: 0.0170 AC: 60 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Bardet-Biedl syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
Cadd	Benign	11
Dann	Benign	0.77
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs80334351; hg19: chr15-73009208;