rs10486541

Positions:

• chr7-33627702-G-A

Variant summary

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

The NM_001348041.4(BBS9):​c.2633-7475G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 152,134 control chromosomes in the GnomAD database, including 4,208 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 (4208 hom., cov: 33)
• Consequence: BBS9 NM_001348041.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0820

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 (EAS) allele frequency at 95% confidence interval = 0.428 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BBS9	NM_001348041.4	c.2633-7475G>A		intron_variant
BBS9	NM_001362679.1	c.2522-7475G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BBS9	ENST00000671952.1	c.2522-7475G>A		intron_variant
BBS9	ENST00000673056.1	c.2633-7475G>A		intron_variant
BBS9	ENST00000672453.1	n.2476+21970G>A		intron_variant, non_coding_transcript_variant
BBS9	ENST00000672758.1	n.191-10062G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32307 AN: 152016 Hom.: 4202 Cov.: 33

Gnomad AFR AF: 0.339

Gnomad AMI AF: 0.229

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.444

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.212

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

GnomAD4 genome AF: 0.212 AC: 32325 AN: 152134 Hom.: 4208 Cov.: 33 AF XY: 0.210 AC XY: 15602 AN XY: 74380

Gnomad4 AFR AF: 0.339

Gnomad4 AMR AF: 0.143

Gnomad4 ASJ AF: 0.235

Gnomad4 EAS AF: 0.444

Gnomad4 SAS AF: 0.224

Gnomad4 FIN AF: 0.103

Gnomad4 NFE AF: 0.148

Gnomad4 OTH AF: 0.209

Alfa AF: 0.166 Hom.: 3059

Bravo AF: 0.221

Asia WGS AF: 0.296 AC: 1027 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	2.0
DANN	Benign	0.82

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10486541; hg19: chr7-33667314;