chr2-169504255-G-C

Variant names:

• chr2-169504255-G-C
• rs72885849
• NM_152384.3:c.901-48G>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.901-48G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0955 in 1,555,378 control chromosomes in the GnomAD database, including 8,170 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.073 (600 hom., cov: 32)
  • Exomes 𝑓: 0.098 (7570 hom.)
• Consequence: BBS5 NM_152384.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.383
• Publications: 6 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=-0.91).
• BP6: Variant 2-169504255-G-C is Benign according to our data. Variant chr2-169504255-G-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 262638.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.11 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BBS5	NM_152384.3	MANE Select	c.901-48G>C		intron	N/A	NP_689597.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BBS5	ENST00000295240.8	TSL:1 MANE Select	c.901-48G>C		intron	N/A	ENSP00000295240.3
	ENSG00000251569	ENST00000513963.1	TSL:2	c.901-48G>C		intron	N/A	ENSP00000424363.1
	BBS5	ENST00000392663.6	TSL:1	c.838-48G>C		intron	N/A	ENSP00000376431.2

Frequencies

GnomAD3 genomes AF: 0.0736 AC: 11190 AN: 152044 Hom.: 601 Cov.: 32

Gnomad AFR AF: 0.0183

Gnomad AMI AF: 0.0989

Gnomad AMR AF: 0.0643

Gnomad ASJ AF: 0.0689

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0314

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.0731

GnomAD2 exomes AF: 0.0771 AC: 19302 AN: 250260 AF XY: 0.0783

Gnomad AFR exome AF: 0.0185

Gnomad AMR exome AF: 0.0476

Gnomad ASJ exome AF: 0.0712

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.108

Gnomad NFE exome AF: 0.112

Gnomad OTH exome AF: 0.0856

GnomAD4 exome AF: 0.0978 AC: 137282 AN: 1403216 Hom.: 7570 Cov.: 26 AF XY: 0.0964 AC XY: 67652 AN XY: 701538

African (AFR) AF: 0.0150 AC: 482 AN: 32224

American (AMR) AF: 0.0496 AC: 2209 AN: 44572

Ashkenazi Jewish (ASJ) AF: 0.0752 AC: 1937 AN: 25752

East Asian (EAS) AF: 0.000127 AC: 5 AN: 39344

South Asian (SAS) AF: 0.0356 AC: 3019 AN: 84768

European-Finnish (FIN) AF: 0.108 AC: 5771 AN: 53304

Middle Eastern (MID) AF: 0.0629 AC: 355 AN: 5648

European-Non Finnish (NFE) AF: 0.112 AC: 118547 AN: 1059086

Other (OTH) AF: 0.0847 AC: 4957 AN: 58518

GnomAD4 genome AF: 0.0735 AC: 11183 AN: 152162 Hom.: 600 Cov.: 32 AF XY: 0.0721 AC XY: 5363 AN XY: 74400

African (AFR) AF: 0.0182 AC: 757 AN: 41540

American (AMR) AF: 0.0642 AC: 982 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0689 AC: 239 AN: 3468

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5184

South Asian (SAS) AF: 0.0314 AC: 151 AN: 4812

European-Finnish (FIN) AF: 0.109 AC: 1146 AN: 10556

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.113 AC: 7650 AN: 67984

Other (OTH) AF: 0.0724 AC: 153 AN: 2114

Alfa AF: 0.0593 Hom.: 87

Bravo AF: 0.0687

Asia WGS AF: 0.0150 AC: 53 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.35
DANN	Benign	0.74
PhyloP100		-0.38
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs72885849; hg19: chr2-170360765;