rs76138485

chr2-169499554-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS1

The NM_152384.3(BBS5):c.750C>T(p.Ile250=) 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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.216

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]

ACMG classification

Verdict is Benign. Variant got -15 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. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BBS5	NM_152384.3	c.750C>T	p.Ile250=	synonymous_variant	9/12	ENST00000295240.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BBS5	ENST00000295240.8	c.750C>T	p.Ile250=	synonymous_variant	9/12	1	NM_152384.3	P1
BBS5	ENST00000392663.6	c.687C>T	p.Ile229=	synonymous_variant	8/11	1
BBS5	ENST00000472667.1	n.521C>T		non_coding_transcript_exon_variant	1/4	2

Frequencies

GnomAD3 genomes AF: 0.00177 AC: 269 AN: 152054 Hom.: 0 Cov.: 32

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.: 0 AF XY: 0.000316 AC XY: 43 AN XY: 135862

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.: 3 Cov.: 31 AF XY: 0.000146 AC XY: 106 AN XY: 726822

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.: 0 Cov.: 32 AF XY: 0.00159 AC XY: 118 AN XY: 74386

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.: 0

Bravo AF: 0.00203

Asia WGS AF: 0.000867 AC: 3 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

Submissions by phenotype

not specified Benign:2

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

Bardet-Biedl syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

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

Other links and lift over

dbSNP: rs76138485; hg19: chr2-170356064; COSMIC: COSV104598702; COSMIC: COSV104598702;