NM_152384.3:c.39C>G

Variant names:

• chr2-169479592-C-G
• rs10188609
• NM_152384.3:c.39C>G

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_152384.3(BBS5):​c.39C>G​(p.Val13Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0075 in 1,614,132 control chromosomes in the GnomAD database, including 843 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.040 (430 hom., cov: 33)
  • Exomes 𝑓: 0.0041 (413 hom.)
• Consequence: BBS5 NM_152384.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.624
• 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: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BP6: Variant 2-169479592-C-G is Benign according to our data. Variant chr2-169479592-C-G is described in ClinVar as Benign. ClinVar VariationId is 262636.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.624 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

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.39C>G	p.Val13Val	synonymous	Exon 1 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.39C>G	p.Val13Val	synonymous	Exon 1 of 12	ENSP00000295240.3	Q8N3I7-1
	ENSG00000251569	ENST00000513963.1	TSL:2	c.39C>G	p.Val13Val	synonymous	Exon 1 of 16	ENSP00000424363.1	E9PBE3
	BBS5	ENST00000392663.6	TSL:1	c.39C>G	p.Val13Val	synonymous	Exon 1 of 11	ENSP00000376431.2	Q8N3I7-2

Frequencies

GnomAD3 genomes AF: 0.0403 AC: 6132 AN: 152172 Hom.: 429 Cov.: 33

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0143

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000323

Gnomad OTH AF: 0.0306

GnomAD2 exomes AF: 0.0104 AC: 2607 AN: 249644 AF XY: 0.00748

Gnomad AFR exome AF: 0.146

Gnomad AMR exome AF: 0.00515

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000214

Gnomad OTH exome AF: 0.00392

GnomAD4 exome AF: 0.00407 AC: 5947 AN: 1461842 Hom.: 413 Cov.: 34 AF XY: 0.00336 AC XY: 2446 AN XY: 727222

African (AFR) AF: 0.151 AC: 5069 AN: 33474

American (AMR) AF: 0.00626 AC: 280 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26134

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39696

South Asian (SAS) AF: 0.000174 AC: 15 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00347 AC: 20 AN: 5768

European-Non Finnish (NFE) AF: 0.0000791 AC: 88 AN: 1111980

Other (OTH) AF: 0.00783 AC: 473 AN: 60390

GnomAD4 genome AF: 0.0404 AC: 6151 AN: 152290 Hom.: 430 Cov.: 33 AF XY: 0.0389 AC XY: 2897 AN XY: 74470

African (AFR) AF: 0.141 AC: 5847 AN: 41560

American (AMR) AF: 0.0142 AC: 217 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000323 AC: 22 AN: 68020

Other (OTH) AF: 0.0303 AC: 64 AN: 2112

Alfa AF: 0.0109 Hom.: 34

Bravo AF: 0.0472

Asia WGS AF: 0.00808 AC: 28 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000296

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Bardet-Biedl syndrome (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	15
DANN	Benign	0.84
PhyloP100		0.62
PromoterAI		-0.027	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs10188609; hg19: chr2-170336102;