2-169479514-G-C

Variant names:

• chr2-169479514-G-C
• rs1879466
• NM_152384.3:c.-40G>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_152384.3(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 NM_152384.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.140
• Publications: 16 publications found

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 Gene-Disease associations (from GenCC):

• Bardet-Biedl syndrome 5

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Genomics England PanelApp, Ambry Genetics, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)
• Bardet-Biedl syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000251569 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 262633.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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 rank	MANE	Protein	UniProt
BBS5	NM_152384.3	c.-40G>C		5_prime_UTR_variant	Exon 1 of 12	ENST00000295240.8	NP_689597.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BBS5	ENST00000295240.8	c.-40G>C		5_prime_UTR_variant	Exon 1 of 12	1	NM_152384.3	ENSP00000295240.3
ENSG00000251569	ENST00000513963.1	c.-40G>C		5_prime_UTR_variant	Exon 1 of 16	2		ENSP00000424363.1

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

GnomAD2 exomes AF: 0.915 AC: 226595 AN: 247568 AF XY: 0.911

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 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

African (AFR) AF: 0.883 AC: 29511 AN: 33438

American (AMR) AF: 0.962 AC: 42999 AN: 44676

Ashkenazi Jewish (ASJ) AF: 0.905 AC: 23655 AN: 26126

East Asian (EAS) AF: 0.984 AC: 39057 AN: 39678

South Asian (SAS) AF: 0.873 AC: 75174 AN: 86148

European-Finnish (FIN) AF: 0.924 AC: 49289 AN: 53366

Middle Eastern (MID) AF: 0.814 AC: 4690 AN: 5760

European-Non Finnish (NFE) AF: 0.911 AC: 1011983 AN: 1110882

Other (OTH) AF: 0.910 AC: 54911 AN: 60344

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

African (AFR) AF: 0.888 AC: 36894 AN: 41564

American (AMR) AF: 0.951 AC: 14555 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.903 AC: 3135 AN: 3472

East Asian (EAS) AF: 0.980 AC: 5051 AN: 5154

South Asian (SAS) AF: 0.881 AC: 4252 AN: 4824

European-Finnish (FIN) AF: 0.932 AC: 9888 AN: 10610

Middle Eastern (MID) AF: 0.884 AC: 260 AN: 294

European-Non Finnish (NFE) AF: 0.906 AC: 61636 AN: 68026

Other (OTH) AF: 0.912 AC: 1929 AN: 2114

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

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

not specified Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Bardet-Biedl syndrome 5 Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.7
DANN	Benign	0.57
PhyloP100		0.14
PromoterAI		-0.14	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1879466; hg19: chr2-170336024;