rs6462461

Positions:

• chr7-33155724-G-A

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
BBS9	NM_198428.3	c.328+22G>A		intron_variant		ENST00000242067.11	NP_940820.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BBS9	ENST00000242067.11	c.328+22G>A		intron_variant		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

GnomAD3 exomes AF: 0.0120 AC: 2339 AN: 194838 Hom.: 407 AF XY: 0.00910 AC XY: 949 AN XY: 104318

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 SAS exome AF: 0.000441

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

Gnomad4 AFR exome AF: 0.152

Gnomad4 AMR exome AF: 0.00709

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000492

Gnomad4 FIN exome AF: 0.0000254

Gnomad4 NFE exome AF: 0.000219

Gnomad4 OTH exome AF: 0.0126

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

Gnomad4 AFR AF: 0.151

Gnomad4 AMR AF: 0.0101

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000531

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000301

Gnomad4 OTH AF: 0.0314

Alfa AF: 0.0273 Hom.: 20

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

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.5
DANN	Benign	0.27

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

Publications

LitVar

Other links and lift over

dbSNP: rs6462461; hg19: chr7-33195336;