rs4723261

chr7-33148184-T-Achr7-33148184-T-Cchr7-33148184-T-G

Variant summary

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

The NM_198428.3(BBS9):c.112+1820T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.877 in 152,238 control chromosomes in the GnomAD database, including 58,819 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 0.88 (58819 hom., cov: 32)
• Consequence: BBS9 NM_198428.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.306

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.963 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BBS9	NM_198428.3	c.112+1820T>A		intron_variant		ENST00000242067.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BBS9	ENST00000242067.11	c.112+1820T>A		intron_variant		1	NM_198428.3	P3

Frequencies

GnomAD3 genomes AF: 0.877 AC: 133372 AN: 152120 Hom.: 58752 Cov.: 32

Gnomad AFR AF: 0.971

Gnomad AMI AF: 0.765

Gnomad AMR AF: 0.889

Gnomad ASJ AF: 0.744

Gnomad EAS AF: 0.709

Gnomad SAS AF: 0.833

Gnomad FIN AF: 0.863

Gnomad MID AF: 0.832

Gnomad NFE AF: 0.844

Gnomad OTH AF: 0.872

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

GnomAD4 genome AF: 0.877 AC: 133500 AN: 152238 Hom.: 58819 Cov.: 32 AF XY: 0.877 AC XY: 65296 AN XY: 74416

Gnomad4 AFR AF: 0.971

Gnomad4 AMR AF: 0.889

Gnomad4 ASJ AF: 0.744

Gnomad4 EAS AF: 0.708

Gnomad4 SAS AF: 0.834

Gnomad4 FIN AF: 0.863

Gnomad4 NFE AF: 0.844

Gnomad4 OTH AF: 0.870

Alfa AF: 0.830 Hom.: 3014

Bravo AF: 0.881

Asia WGS AF: 0.772 AC: 2685 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	1.1
Dann	Benign	0.83

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: rs4723261; hg19: chr7-33187796;