rs4236337

Positions:

• chr7-33467294-C-A
• chr7-33467294-C-G
• chr7-33467294-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.2116-38169C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.751 in 151,916 control chromosomes in the GnomAD database, including 43,230 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 0.75 (43230 hom., cov: 30)
• Consequence: BBS9 NM_198428.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.170

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=-0.63).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.847 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BBS9	NM_198428.3	c.2116-38169C>A		intron_variant		ENST00000242067.11	NP_940820.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BBS9	ENST00000242067.11	c.2116-38169C>A		intron_variant		1	NM_198428.3	ENSP00000242067	P3

Frequencies

GnomAD3 genomes AF: 0.750 AC: 113895 AN: 151798 Hom.: 43165 Cov.: 30

Gnomad AFR AF: 0.855

Gnomad AMI AF: 0.538

Gnomad AMR AF: 0.788

Gnomad ASJ AF: 0.650

Gnomad EAS AF: 0.722

Gnomad SAS AF: 0.790

Gnomad FIN AF: 0.786

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.680

Gnomad OTH AF: 0.760

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

GnomAD4 genome AF: 0.751 AC: 114019 AN: 151916 Hom.: 43230 Cov.: 30 AF XY: 0.759 AC XY: 56349 AN XY: 74280

Gnomad4 AFR AF: 0.855

Gnomad4 AMR AF: 0.788

Gnomad4 ASJ AF: 0.650

Gnomad4 EAS AF: 0.721

Gnomad4 SAS AF: 0.791

Gnomad4 FIN AF: 0.786

Gnomad4 NFE AF: 0.680

Gnomad4 OTH AF: 0.759

Alfa AF: 0.701 Hom.: 11941

Bravo AF: 0.755

Asia WGS AF: 0.752 AC: 2614 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	6.6
DANN	Benign	0.84

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: rs4236337; hg19: chr7-33506906;