Variant chr2-169499554-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_152384.3(BBS5):c.750C>T(p.Ile250Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000331 in 1,613,020 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0018 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00018 ( 3 hom. )

Consequence

BBS5
NM_152384.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.216

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:

ENSG00000251569 (HGNC:):

ENSG00000251569 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.36).

BP6

Variant 2-169499554-C-T is Benign according to our data. Variant chr2-169499554-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 281598.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-169499554-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.216 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00177 (269/152168) while in subpopulation AFR AF= 0.00609 (253/41516). AF 95% confidence interval is 0.00548. There are 0 homozygotes in gnomad4. There are 118 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BBS5	NM_152384.3 linkuse as main transcript	c.750C>T	p.Ile250Ile	synonymous_variant	9/12	ENST00000295240.8	NP_689597.1	Q8N3I7-1A0A0S2Z626

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
BBS5	ENST00000295240.8 linkuse as main transcript	c.750C>T	p.Ile250Ile	synonymous_variant	9/12	1	NM_152384.3	ENSP00000295240.3	Q8N3I7-1
ENSG00000251569	ENST00000513963.1 linkuse as main transcript	c.750C>T	p.Ile250Ile	synonymous_variant	9/16	2		ENSP00000424363.1	E9PBE3
BBS5	ENST00000392663.6 linkuse as main transcript	c.687C>T	p.Ile229Ile	synonymous_variant	8/11	1		ENSP00000376431.2	Q8N3I7-2
BBS5	ENST00000472667.1 linkuse as main transcript	n.521C>T		non_coding_transcript_exon_variant	1/4	2

Frequencies

GnomAD3 genomes

AF:

0.00177

AC:

269

AN:

152054

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00611

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000786

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000959

GnomAD3 exomes

AF:

0.000446

AC:

112

AN:

251372

Hom.:

AF XY:

0.000316

AC XY:

AN XY:

135862

show subpopulations

Gnomad AFR exome

AF:

0.00646

Gnomad AMR exome

AF:

0.000174

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000181

AC:

265

AN:

1460852

Hom.:

Cov.:

AF XY:

0.000146

AC XY:

106

AN XY:

726822

show subpopulations

Gnomad4 AFR exome

AF:

0.00685

Gnomad4 AMR exome

AF:

0.000201

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.000315

GnomAD4 genome

AF:

0.00177

AC:

269

AN:

152168

Hom.:

Cov.:

AF XY:

0.00159

AC XY:

118

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.00609

Gnomad4 AMR

AF:

0.000785

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000949

Alfa

AF:

0.000904

Hom.:

Bravo

AF:

0.00203

Asia WGS

AF:

0.000867

AC:

AN:

3474

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Mar 31, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jun 17, 2015	- -

Bardet-Biedl syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 30, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

CADD

Benign

7.5

DANN

Benign

0.70

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