chr2-169479514-G-C

Position:

• chr2-169479514-G-C

Variant summary

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

The ENST00000295240.8(BBS5):​c.-40G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.911 in 1,612,696 control chromosomes in the GnomAD database, including 670,282 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.91 (62971 hom., cov: 34)
  • Exomes 𝑓: 0.91 (607311 hom.)
• Consequence: BBS5 ENST00000295240.8 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.140

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 2-169479514-G-C is Benign according to our data. Variant chr2-169479514-G-C is described in ClinVar as [Benign]. Clinvar id is 262633.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-169479514-G-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.957 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BBS5	NM_152384.3	c.-40G>C		5_prime_UTR_variant	1/12	ENST00000295240.8	NP_689597.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BBS5	ENST00000295240.8	c.-40G>C		5_prime_UTR_variant	1/12	1	NM_152384.3	ENSP00000295240	P1
BBS5	ENST00000392663.6	c.-40G>C		5_prime_UTR_variant	1/11	1		ENSP00000376431
BBS5	ENST00000469980.1	n.35G>C		non_coding_transcript_exon_variant	1/2	4
BBS5	ENST00000443151.1	c.-40G>C		5_prime_UTR_variant, NMD_transcript_variant	1/6	5		ENSP00000406182

Frequencies

GnomAD3 genomes AF: 0.909 AC: 138321 AN: 152160 Hom.: 62931 Cov.: 34

Gnomad AFR AF: 0.888

Gnomad AMI AF: 0.898

Gnomad AMR AF: 0.951

Gnomad ASJ AF: 0.903

Gnomad EAS AF: 0.980

Gnomad SAS AF: 0.882

Gnomad FIN AF: 0.932

Gnomad MID AF: 0.877

Gnomad NFE AF: 0.906

Gnomad OTH AF: 0.911

GnomAD3 exomes AF: 0.915 AC: 226595 AN: 247568 Hom.: 103844 AF XY: 0.911 AC XY: 122226 AN XY: 134126

Gnomad AFR exome AF: 0.891

Gnomad AMR exome AF: 0.965

Gnomad ASJ exome AF: 0.901

Gnomad EAS exome AF: 0.980

Gnomad SAS exome AF: 0.873

Gnomad FIN exome AF: 0.926

Gnomad NFE exome AF: 0.903

Gnomad OTH exome AF: 0.915

GnomAD4 exome AF: 0.912 AC: 1331269 AN: 1460418 Hom.: 607311 Cov.: 35 AF XY: 0.910 AC XY: 660863 AN XY: 726564

Gnomad4 AFR exome AF: 0.883

Gnomad4 AMR exome AF: 0.962

Gnomad4 ASJ exome AF: 0.905

Gnomad4 EAS exome AF: 0.984

Gnomad4 SAS exome AF: 0.873

Gnomad4 FIN exome AF: 0.924

Gnomad4 NFE exome AF: 0.911

Gnomad4 OTH exome AF: 0.910

GnomAD4 genome AF: 0.909 AC: 138419 AN: 152278 Hom.: 62971 Cov.: 34 AF XY: 0.911 AC XY: 67840 AN XY: 74446

Gnomad4 AFR AF: 0.888

Gnomad4 AMR AF: 0.951

Gnomad4 ASJ AF: 0.903

Gnomad4 EAS AF: 0.980

Gnomad4 SAS AF: 0.881

Gnomad4 FIN AF: 0.932

Gnomad4 NFE AF: 0.906

Gnomad4 OTH AF: 0.912

Alfa AF: 0.896 Hom.: 11184

Bravo AF: 0.912

Asia WGS AF: 0.936 AC: 3256 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Bardet-Biedl syndrome 5 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.7
DANN	Benign	0.57

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: rs1879466; hg19: chr2-170336024;