rs767240340

Variant names:

• chr2-169492949-G-C
• rs767240340
• NM_152384.3:c.462G>C

Your query was ambiguous. Multiple possible variants found:

• chr2-169492949-G-C
• chr2-169492949-G-T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_152384.3(BBS5):​c.462G>C​(p.Leu154Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,140 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: BBS5 NM_152384.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.646
• Publications: 1 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: Genomics England PanelApp, Ambry Genetics, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, G2P
• BBS5-related ciliopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• Bardet-Biedl syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000251569 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 2-169492949-G-C is Benign according to our data. Variant chr2-169492949-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 531838.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.646 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152384.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BBS5	NM_152384.3	MANE Select	c.462G>C	p.Leu154Leu	synonymous	Exon 6 of 12	NP_689597.1	A0A0S2Z626

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BBS5	ENST00000295240.8	TSL:1 MANE Select	c.462G>C	p.Leu154Leu	synonymous	Exon 6 of 12	ENSP00000295240.3	Q8N3I7-1
	ENSG00000251569	ENST00000513963.1	TSL:2	c.462G>C	p.Leu154Leu	synonymous	Exon 6 of 16	ENSP00000424363.1	E9PBE3
	BBS5	ENST00000392663.6	TSL:1	c.462G>C	p.Leu154Leu	synonymous	Exon 6 of 11	ENSP00000376431.2	Q8N3I7-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000239 AC: 6 AN: 251370 AF XY: 0.0000147

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461140 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 726924

African (AFR) AF: 0.00 AC: 0 AN: 33454

American (AMR) AF: 0.000134 AC: 6 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26112

East Asian (EAS) AF: 0.00 AC: 0 AN: 39582

South Asian (SAS) AF: 0.00 AC: 0 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5740

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111524

Other (OTH) AF: 0.0000166 AC: 1 AN: 60362

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Bardet-Biedl syndrome (1)
-	-	1	BBS5-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	5.3
DANN	Benign	0.74
PhyloP100		0.65
Mutation Taster		=100/0	polymorphism

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: rs767240340; hg19: chr2-170349459;