rs17727583

Variant names:

• chr7-33533934-A-C
• rs17727583
• NM_198428.3:c.2299-20A>C

Your query was ambiguous. Multiple possible variants found:

• chr7-33533934-A-C
• chr7-33533934-A-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_198428.3(BBS9):​c.2299-20A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0122 in 1,613,594 control chromosomes in the GnomAD database, including 149 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0098 (13 hom., cov: 32)
  • Exomes 𝑓: 0.012 (136 hom.)
• Consequence: BBS9 NM_198428.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.0740
• Publications: 6 publications found

Genes affected

BBS9 (HGNC:30000): (Bardet-Biedl syndrome 9) This gene is downregulated by parathyroid hormone in osteoblastic cells, and therefore is thought to be involved in parathyroid hormone action in bones. The exact function of this gene has not yet been determined. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jan 2017]

BBS9 Gene-Disease associations (from GenCC):

• Bardet-Biedl syndrome 9

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp
• BBS9-related ciliopathy

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

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 7-33533934-A-C is Benign according to our data. Variant chr7-33533934-A-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 263124.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00981 (1495/152338) while in subpopulation NFE AF = 0.0144 (980/68022). AF 95% confidence interval is 0.0137. There are 13 homozygotes in GnomAd4. There are 717 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 13 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198428.3. 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
	BBS9	NM_198428.3	MANE Select	c.2299-20A>C		intron	N/A	NP_940820.1	Q3SYG4-1
	BBS9	NM_001348041.4		c.2299-20A>C		intron	N/A	NP_001334970.1	A0A5F9ZH14
	BBS9	NM_001348036.1		c.2299-20A>C		intron	N/A	NP_001334965.1	Q3SYG4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BBS9	ENST00000242067.11	TSL:1 MANE Select	c.2299-20A>C		intron	N/A	ENSP00000242067.6	Q3SYG4-1
	BBS9	ENST00000434373.3	TSL:1	c.997-20A>C		intron	N/A	ENSP00000388114.1	H7BZ69
	BBS9	ENST00000433714.5	TSL:1	n.*1060-20A>C		intron	N/A	ENSP00000412159.1	F8WCG5

Frequencies

GnomAD3 genomes AF: 0.00982 AC: 1495 AN: 152220 Hom.: 13 Cov.: 32

Gnomad AFR AF: 0.00265

Gnomad AMI AF: 0.0833

Gnomad AMR AF: 0.0143

Gnomad ASJ AF: 0.0130

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.00188

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0144

Gnomad OTH AF: 0.0148

GnomAD2 exomes AF: 0.00923 AC: 2320 AN: 251404 AF XY: 0.00929

Gnomad AFR exome AF: 0.00197

Gnomad AMR exome AF: 0.00720

Gnomad ASJ exome AF: 0.0138

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00402

Gnomad NFE exome AF: 0.0146

Gnomad OTH exome AF: 0.0137

GnomAD4 exome AF: 0.0125 AC: 18202 AN: 1461256 Hom.: 136 Cov.: 30 AF XY: 0.0122 AC XY: 8903 AN XY: 726988

African (AFR) AF: 0.00209 AC: 70 AN: 33466

American (AMR) AF: 0.00762 AC: 341 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0134 AC: 350 AN: 26134

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00259 AC: 223 AN: 86242

European-Finnish (FIN) AF: 0.00449 AC: 240 AN: 53410

Middle Eastern (MID) AF: 0.0158 AC: 91 AN: 5764

European-Non Finnish (NFE) AF: 0.0145 AC: 16116 AN: 1111438

Other (OTH) AF: 0.0128 AC: 770 AN: 60378

GnomAD4 genome AF: 0.00981 AC: 1495 AN: 152338 Hom.: 13 Cov.: 32 AF XY: 0.00962 AC XY: 717 AN XY: 74504

African (AFR) AF: 0.00265 AC: 110 AN: 41584

American (AMR) AF: 0.0142 AC: 218 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0130 AC: 45 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00186 AC: 9 AN: 4830

European-Finnish (FIN) AF: 0.00188 AC: 20 AN: 10620

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0144 AC: 980 AN: 68022

Other (OTH) AF: 0.0147 AC: 31 AN: 2116

Alfa AF: 0.00654 Hom.: 2

Bravo AF: 0.0108

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	Bardet-Biedl syndrome 1 (4)
-	-	1	Bardet-Biedl syndrome (1)
-	-	1	Bardet-Biedl syndrome 9 (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.6
DANN	Benign	0.72
PhyloP100		-0.074
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: rs17727583; hg19: chr7-33573546;