rs10254116

Positions:

• chr7-33197877-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_198428.3(BBS9):​c.442+20286T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 151,710 control chromosomes in the GnomAD database, including 8,866 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.34 (8866 hom., cov: 31)
• Consequence: BBS9 NM_198428.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.948

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BBS9	NM_198428.3	c.442+20286T>C		intron_variant		ENST00000242067.11	NP_940820.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BBS9	ENST00000242067.11	c.442+20286T>C		intron_variant		1	NM_198428.3	ENSP00000242067.6

Frequencies

GnomAD3 genomes AF: 0.336 AC: 50946 AN: 151594 Hom.: 8861 Cov.: 31

Gnomad AFR AF: 0.312

Gnomad AMI AF: 0.253

Gnomad AMR AF: 0.464

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.307

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.384

Gnomad MID AF: 0.295

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.348

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.336 AC: 50968 AN: 151710 Hom.: 8866 Cov.: 31 AF XY: 0.342 AC XY: 25394 AN XY: 74146

Gnomad4 AFR AF: 0.312

Gnomad4 AMR AF: 0.465

Gnomad4 ASJ AF: 0.264

Gnomad4 EAS AF: 0.307

Gnomad4 SAS AF: 0.229

Gnomad4 FIN AF: 0.384

Gnomad4 NFE AF: 0.329

Gnomad4 OTH AF: 0.345

Alfa AF: 0.328 Hom.: 15599

Bravo AF: 0.342

Asia WGS AF: 0.265 AC: 909 AN: 3430

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	14
DANN	Benign	0.92

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: rs10254116; hg19: chr7-33237489;