rs6462461

Variant names:

• chr7-33155724-G-A
• rs6462461
• NM_198428.3:c.328+22G>A

Variant summary

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

The NM_198428.3(BBS9):​c.328+22G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00912 in 1,092,354 control chromosomes in the GnomAD database, including 1,267 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.045 (504 hom., cov: 29)
  • Exomes 𝑓: 0.0050 (763 hom.)
• Consequence: BBS9 NM_198428.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.315
• Publications: 1 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: G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• 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=-0.85).
• BP6: Variant 7-33155724-G-A is Benign according to our data. Variant chr7-33155724-G-A is described in ClinVar as Benign. ClinVar VariationId is 263129.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BBS9	NM_198428.3	c.328+22G>A		intron_variant	Intron 4 of 22	ENST00000242067.11	NP_940820.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BBS9	ENST00000242067.11	c.328+22G>A		intron_variant	Intron 4 of 22	1	NM_198428.3	ENSP00000242067.6

Frequencies

GnomAD3 genomes AF: 0.0447 AC: 5004 AN: 111910 Hom.: 502 Cov.: 29

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0102

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000795

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0132

Gnomad NFE AF: 0.000301

Gnomad OTH AF: 0.0319

GnomAD2 exomes AF: 0.0120 AC: 2339 AN: 194838 AF XY: 0.00910

Gnomad AFR exome AF: 0.158

Gnomad AMR exome AF: 0.00543

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000458

Gnomad OTH exome AF: 0.00696

GnomAD4 exome AF: 0.00503 AC: 4933 AN: 980338 Hom.: 763 Cov.: 19 AF XY: 0.00432 AC XY: 2144 AN XY: 496758

African (AFR) AF: 0.152 AC: 3903 AN: 25598

American (AMR) AF: 0.00709 AC: 285 AN: 40196

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20628

East Asian (EAS) AF: 0.00 AC: 0 AN: 31954

South Asian (SAS) AF: 0.000492 AC: 36 AN: 73220

European-Finnish (FIN) AF: 0.0000254 AC: 1 AN: 39364

Middle Eastern (MID) AF: 0.00665 AC: 28 AN: 4210

European-Non Finnish (NFE) AF: 0.000219 AC: 154 AN: 703432

Other (OTH) AF: 0.0126 AC: 526 AN: 41736

GnomAD4 genome AF: 0.0449 AC: 5029 AN: 112016 Hom.: 504 Cov.: 29 AF XY: 0.0429 AC XY: 2392 AN XY: 55736

African (AFR) AF: 0.151 AC: 4835 AN: 32120

American (AMR) AF: 0.0101 AC: 125 AN: 12342

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2686

East Asian (EAS) AF: 0.00 AC: 0 AN: 4014

South Asian (SAS) AF: 0.000531 AC: 2 AN: 3766

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8284

Middle Eastern (MID) AF: 0.0146 AC: 3 AN: 206

European-Non Finnish (NFE) AF: 0.000301 AC: 14 AN: 46510

Other (OTH) AF: 0.0314 AC: 50 AN: 1590

Alfa AF: 0.0313 Hom.: 28

Bravo AF: 0.0391

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Jun 19, 2021

GeneDx

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	-0.85
CADD	Benign	6.5
DANN	Benign	0.27
PhyloP100		-0.32
Mutation Taster		=100/0	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: rs6462461; hg19: chr7-33195336;