7-33295780-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_198428.3(BBS9):c.1016+21824C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0199 in 152,050 control chromosomes in the GnomAD database, including 52 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 0.020 (52 hom., cov: 32)
• Consequence: BBS9 NM_198428.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39

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=-0.91).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0199 (3028/152050) while in subpopulation NFE AF= 0.0302 (2049/67900). AF 95% confidence interval is 0.0291. There are 52 homozygotes in gnomad4. There are 1475 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 52 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BBS9	NM_198428.3	c.1016+21824C>T		intron_variant		ENST00000242067.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BBS9	ENST00000242067.11	c.1016+21824C>T		intron_variant		1	NM_198428.3	P3

Frequencies

GnomAD3 genomes AF: 0.0199 AC: 3027 AN: 151932 Hom.: 52 Cov.: 32

Gnomad AFR AF: 0.00524

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.0138

Gnomad ASJ AF: 0.0228

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0133

Gnomad FIN AF: 0.0326

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.0302

Gnomad OTH AF: 0.0173

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

GnomAD4 genome AF: 0.0199 AC: 3028 AN: 152050 Hom.: 52 Cov.: 32 AF XY: 0.0198 AC XY: 1475 AN XY: 74342

Gnomad4 AFR AF: 0.00523

Gnomad4 AMR AF: 0.0138

Gnomad4 ASJ AF: 0.0228

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0137

Gnomad4 FIN AF: 0.0326

Gnomad4 NFE AF: 0.0302

Gnomad4 OTH AF: 0.0166

Alfa AF: 0.00575 Hom.: 2

Bravo AF: 0.0181

Asia WGS AF: 0.00494 AC: 18 AN: 3456

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.27
Dann	Benign	0.22

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: rs10486526; hg19: chr7-33335392;