rs145968663

chr15-72735202-T-C

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.1106+20T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00259 in 1,602,952 control chromosomes in the GnomAD database, including 162 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0048 (20 hom., cov: 32)
  • Exomes 𝑓: 0.0024 (142 hom.)
• Consequence: BBS4 NM_033028.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.220

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=-0.88).
• BP6: Variant 15-72735202-T-C is Benign according to our data. Variant chr15-72735202-T-C is described in ClinVar as [Benign]. Clinvar id is 262134.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-72735202-T-C is described in Lovd as [Benign].
• BA1: GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0681 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BBS4	NM_033028.5	c.1106+20T>C		intron_variant		ENST00000268057.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BBS4	ENST00000268057.9	c.1106+20T>C		intron_variant		1	NM_033028.5	P1

Frequencies

GnomAD3 genomes AF: 0.00474 AC: 721 AN: 152194 Hom.: 18 Cov.: 32

Gnomad AFR AF: 0.00154

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0399

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00404

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00907

GnomAD3 exomes AF: 0.0108 AC: 2713 AN: 250872 Hom.: 122 AF XY: 0.00799 AC XY: 1083 AN XY: 135594

Gnomad AFR exome AF: 0.00154

Gnomad AMR exome AF: 0.0738

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00458

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000529

Gnomad OTH exome AF: 0.00947

GnomAD4 exome AF: 0.00236 AC: 3424 AN: 1450640 Hom.: 142 Cov.: 27 AF XY: 0.00194 AC XY: 1398 AN XY: 722378

Gnomad4 AFR exome AF: 0.000932

Gnomad4 AMR exome AF: 0.0702

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00167

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000499

Gnomad4 OTH exome AF: 0.00237

GnomAD4 genome AF: 0.00479 AC: 729 AN: 152312 Hom.: 20 Cov.: 32 AF XY: 0.00481 AC XY: 358 AN XY: 74490

Gnomad4 AFR AF: 0.00154

Gnomad4 AMR AF: 0.0404

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00405

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.00851

Alfa AF: 0.00316 Hom.: 0

Bravo AF: 0.00863

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Bardet-Biedl syndrome 4 Benign:1

Benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Apr 21, 2022

- -

Bardet-Biedl syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.65
Dann	Benign	0.59
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs145968663; hg19: chr15-73027543;