7-33587247-C-T

Variant summary

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

The NM_198428.3(BBS9):c.2522-17618C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 151,766 control chromosomes in the GnomAD database, including 16,976 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 0.40 (16976 hom., cov: 31)
• Consequence: BBS9 NM_198428.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.172

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.781 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BBS9	NM_198428.3	c.2522-17618C>T		intron_variant		ENST00000242067.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BBS9	ENST00000242067.11	c.2522-17618C>T		intron_variant		1	NM_198428.3	P3

Frequencies

GnomAD3 genomes AF: 0.402 AC: 61034 AN: 151650 Hom.: 16933 Cov.: 31

Gnomad AFR AF: 0.787

Gnomad AMI AF: 0.307

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.314

Gnomad EAS AF: 0.479

Gnomad SAS AF: 0.410

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.232

Gnomad OTH AF: 0.380

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

GnomAD4 genome AF: 0.403 AC: 61122 AN: 151766 Hom.: 16976 Cov.: 31 AF XY: 0.401 AC XY: 29729 AN XY: 74148

Gnomad4 AFR AF: 0.788

Gnomad4 AMR AF: 0.258

Gnomad4 ASJ AF: 0.314

Gnomad4 EAS AF: 0.478

Gnomad4 SAS AF: 0.410

Gnomad4 FIN AF: 0.207

Gnomad4 NFE AF: 0.232

Gnomad4 OTH AF: 0.378

Alfa AF: 0.265 Hom.: 2430

Bravo AF: 0.422

Asia WGS AF: 0.433 AC: 1506 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.80
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: rs1985080; hg19: chr7-33626859;