rs17724206

Positions:

• chr7-33384149-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198428.3(BBS9):​c.1962+311G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 152,146 control chromosomes in the GnomAD database, including 4,053 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 0.21 (4053 hom., cov: 32)
• Consequence: BBS9 NM_198428.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.60

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BBS9	NM_198428.3	c.1962+311G>A		intron_variant		ENST00000242067.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BBS9	ENST00000242067.11	c.1962+311G>A		intron_variant		1	NM_198428.3	P3

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31824 AN: 152028 Hom.: 4048 Cov.: 32

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.351

Gnomad ASJ AF: 0.194

Gnomad EAS AF: 0.0337

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.283

Gnomad MID AF: 0.229

Gnomad NFE AF: 0.251

Gnomad OTH AF: 0.231

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

GnomAD4 genome AF: 0.209 AC: 31840 AN: 152146 Hom.: 4053 Cov.: 32 AF XY: 0.214 AC XY: 15945 AN XY: 74374

Gnomad4 AFR AF: 0.101

Gnomad4 AMR AF: 0.352

Gnomad4 ASJ AF: 0.194

Gnomad4 EAS AF: 0.0340

Gnomad4 SAS AF: 0.131

Gnomad4 FIN AF: 0.283

Gnomad4 NFE AF: 0.251

Gnomad4 OTH AF: 0.229

Alfa AF: 0.244 Hom.: 9834

Bravo AF: 0.211

Asia WGS AF: 0.0840 AC: 291 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.038
DANN	Benign	0.58

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: rs17724206; hg19: chr7-33423761;