chr7-33633653-G-T

Position:

• chr7-33633653-G-T

Variant summary

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

The NM_001348041.4(BBS9):​c.2633-1524G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0641 in 151,970 control chromosomes in the GnomAD database, including 1,001 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 0.064 (1001 hom., cov: 31)
• Consequence: BBS9 NM_001348041.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.267

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BBS9	NM_001348041.4	c.2633-1524G>T		intron_variant			NP_001334970.1
BBS9	NM_001362679.1	c.2522-1524G>T		intron_variant			NP_001349608.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BBS9	ENST00000673056.1	c.2633-1524G>T		intron_variant				ENSP00000499989.1
BBS9	ENST00000671952.1	c.2522-1524G>T		intron_variant				ENSP00000500239.1
BBS9	ENST00000672453.1	n.2476+27921G>T		intron_variant
BBS9	ENST00000672758.1	n.191-4111G>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.0640 AC: 9712 AN: 151856 Hom.: 984 Cov.: 31

Gnomad AFR AF: 0.0146

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.0424

Gnomad EAS AF: 0.401

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.0575

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0326

Gnomad OTH AF: 0.0617

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

GnomAD4 genome AF: 0.0641 AC: 9748 AN: 151970 Hom.: 1001 Cov.: 31 AF XY: 0.0723 AC XY: 5373 AN XY: 74286

Gnomad4 AFR AF: 0.0146

Gnomad4 AMR AF: 0.218

Gnomad4 ASJ AF: 0.0424

Gnomad4 EAS AF: 0.401

Gnomad4 SAS AF: 0.129

Gnomad4 FIN AF: 0.0575

Gnomad4 NFE AF: 0.0326

Gnomad4 OTH AF: 0.0672

Alfa AF: 0.0460 Hom.: 1048

Bravo AF: 0.0754

Asia WGS AF: 0.270 AC: 936 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.3
DANN	Benign	0.64

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs17170316; hg19: chr7-33673265;