rs141170836

Positions:

• chr16-56484748-G-A
• chr16-56484748-G-C
• chr16-56484748-G-T

Variant summary

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

The NM_031885.5(BBS2):​c.*13C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00387 in 1,609,052 control chromosomes in the GnomAD database, including 169 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0063 (17 hom., cov: 32)
  • Exomes 𝑓: 0.0036 (152 hom.)
• Consequence: BBS2 NM_031885.5 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -4.00

Genes affected

BBS2 (HGNC:967): (Bardet-Biedl syndrome 2) 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 and the similar phenotypes exhibited by mutations in BBS gene family members is likely due to their 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 forms a multiprotein BBSome complex with seven other BBS proteins.[provided by RefSeq, Oct 2014]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 16-56484748-G-A is Benign according to our data. Variant chr16-56484748-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 261976.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0682 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BBS2	NM_031885.5	c.*13C>T		3_prime_UTR_variant	17/17	ENST00000245157.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BBS2	ENST00000245157.11	c.*13C>T		3_prime_UTR_variant	17/17	1	NM_031885.5	P1

Frequencies

GnomAD3 genomes AF: 0.00633 AC: 963 AN: 152152 Hom.: 17 Cov.: 32

Gnomad AFR AF: 0.000893

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0426

Gnomad ASJ AF: 0.000867

Gnomad EAS AF: 0.0210

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.0115

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000353

Gnomad OTH AF: 0.00669

GnomAD3 exomes AF: 0.0128 AC: 3223 AN: 250980 Hom.: 94 AF XY: 0.0100 AC XY: 1360 AN XY: 135648

Gnomad AFR exome AF: 0.000493

Gnomad AMR exome AF: 0.0735

Gnomad ASJ exome AF: 0.000497

Gnomad EAS exome AF: 0.0203

Gnomad SAS exome AF: 0.000688

Gnomad FIN exome AF: 0.00865

Gnomad NFE exome AF: 0.000352

Gnomad OTH exome AF: 0.00914

GnomAD4 exome AF: 0.00362 AC: 5269 AN: 1456782 Hom.: 152 Cov.: 29 AF XY: 0.00327 AC XY: 2373 AN XY: 725032

Gnomad4 AFR exome AF: 0.000540

Gnomad4 AMR exome AF: 0.0702

Gnomad4 ASJ exome AF: 0.000499

Gnomad4 EAS exome AF: 0.0279

Gnomad4 SAS exome AF: 0.000569

Gnomad4 FIN exome AF: 0.00887

Gnomad4 NFE exome AF: 0.000190

Gnomad4 OTH exome AF: 0.00435

GnomAD4 genome AF: 0.00632 AC: 962 AN: 152270 Hom.: 17 Cov.: 32 AF XY: 0.00731 AC XY: 544 AN XY: 74460

Gnomad4 AFR AF: 0.000890

Gnomad4 AMR AF: 0.0425

Gnomad4 ASJ AF: 0.000867

Gnomad4 EAS AF: 0.0210

Gnomad4 SAS AF: 0.000829

Gnomad4 FIN AF: 0.0115

Gnomad4 NFE AF: 0.000353

Gnomad4 OTH AF: 0.00662

Alfa AF: 0.00110 Hom.: 0

Bravo AF: 0.00883

Asia WGS AF: 0.0130 AC: 46 AN: 3478

ClinVar

Significance: Benign/Likely 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	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Feb 13, 2017	Variant summary: The BBS2 c.*13C>T variant involves the alteration of a non-conserved nucleotide located in 3-prime untranslated region of exon 17. Mutation taster predicts a benign outcome for this variant. This variant was found in 1175/118352 control chromosomes (including 35 homozygotes), predominantly observed in the Latino subpopulation at a frequency of 0.077996 (872/11180). This frequency is about 92 times the estimated maximal expected allele frequency of a pathogenic BBS2 variant (0.0008452), suggesting this is a benign polymorphism found primarily in the populations of Latino origin. In addition, multiple clinical diagnostic laboratories/reputable databases have classified this variant as likely benign/benign. Taken together, this variant is classified as Benign. -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 23, 2021	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Bardet-Biedl syndrome 2 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.029
DANN	Benign	0.56
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs141170836; hg19: chr16-56518660;