Variant 2-169482299-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000295240.8(BBS5):c.108C>T(p.Ser36=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00497 in 1,607,916 control chromosomes in the GnomAD database, including 349 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. S36S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.027 ( 191 hom., cov: 33)

Exomes 𝑓: 0.0027 ( 158 hom. )

Consequence

BBS5
ENST00000295240.8 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.149

Variant links:

Genes affected

BBS5 (HGNC:970): (Bardet-Biedl syndrome 5) This gene encodes a protein that has been directly linked to Bardet-Biedl syndrome. The primary features of this syndrome include retinal dystrophy, obesity, polydactyly, renal abnormalities and learning disabilities. Experimentation in non-human eukaryotes suggests that this gene is expressed in ciliated cells and that it is required for the formation of cilia. Alternate transcriptional splice variants have been observed but have not been fully characterized. [provided by RefSeq, Jul 2008]

BBS5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 2-169482299-C-T is Benign according to our data. Variant chr2-169482299-C-T is described in ClinVar as [Benign]. Clinvar id is 262634.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-169482299-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.149 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0913 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BBS5	NM_152384.3 linkuse as main transcript	c.108C>T	p.Ser36=	synonymous_variant	2/12	ENST00000295240.8	NP_689597.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BBS5	ENST00000295240.8 linkuse as main transcript	c.108C>T	p.Ser36=	synonymous_variant	2/12	1	NM_152384.3	ENSP00000295240	P1	Q8N3I7-1
BBS5	ENST00000392663.6 linkuse as main transcript	c.108C>T	p.Ser36=	synonymous_variant	2/11	1		ENSP00000376431		Q8N3I7-2
BBS5	ENST00000469980.1 linkuse as main transcript	n.182C>T		non_coding_transcript_exon_variant	2/2	4
BBS5	ENST00000443151.1 linkuse as main transcript	c.108C>T	p.Ser36=	synonymous_variant, NMD_transcript_variant	2/6	5		ENSP00000406182

Frequencies

GnomAD3 genomes

AF:

0.0271

AC:

4115

AN:

152032

Hom.:

191

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0940

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0114

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000338

Gnomad OTH

AF:

0.0120

GnomAD3 exomes

AF:

0.00660

AC:

1659

AN:

251266

Hom.:

AF XY:

0.00460

AC XY:

625

AN XY:

135826

show subpopulations

Gnomad AFR exome

AF:

0.0910

Gnomad AMR exome

AF:

0.00393

Gnomad ASJ exome

AF:

0.000496

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000202

Gnomad OTH exome

AF:

0.00294

GnomAD4 exome

AF:

0.00266

AC:

3873

AN:

1455766

Hom.:

158

Cov.:

AF XY:

0.00229

AC XY:

1658

AN XY:

724634

show subpopulations

Gnomad4 AFR exome

AF:

0.0942

Gnomad4 AMR exome

AF:

0.00474

Gnomad4 ASJ exome

AF:

0.000421

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000174

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000119

Gnomad4 OTH exome

AF:

0.00595

GnomAD4 genome

AF:

0.0271

AC:

4119

AN:

152150

Hom.:

191

Cov.:

AF XY:

0.0255

AC XY:

1895

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.0938

Gnomad4 AMR

AF:

0.0114

Gnomad4 ASJ

AF:

0.000577

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000416

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000338

Gnomad4 OTH

AF:

0.0119

Alfa

AF:

0.0119

Hom.:

Bravo

AF:

0.0301

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Bardet-Biedl syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

6.6

DANN

Benign

0.68

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over