7-33466937-T-G

Position:

• chr7-33466937-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.2116-38526T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.752 in 151,868 control chromosomes in the GnomAD database, including 43,348 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 (43348 hom., cov: 30)
• Consequence: BBS9 NM_198428.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.100

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).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.845 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BBS9	NM_198428.3	c.2116-38526T>G		intron_variant		ENST00000242067.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BBS9	ENST00000242067.11	c.2116-38526T>G		intron_variant		1	NM_198428.3	P3

Frequencies

GnomAD3 genomes AF: 0.752 AC: 114056 AN: 151748 Hom.: 43282 Cov.: 30

Gnomad AFR AF: 0.852

Gnomad AMI AF: 0.536

Gnomad AMR AF: 0.789

Gnomad ASJ AF: 0.653

Gnomad EAS AF: 0.722

Gnomad SAS AF: 0.792

Gnomad FIN AF: 0.787

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.683

Gnomad OTH AF: 0.762

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

GnomAD4 genome AF: 0.752 AC: 114182 AN: 151868 Hom.: 43348 Cov.: 30 AF XY: 0.760 AC XY: 56391 AN XY: 74242

Gnomad4 AFR AF: 0.853

Gnomad4 AMR AF: 0.789

Gnomad4 ASJ AF: 0.653

Gnomad4 EAS AF: 0.722

Gnomad4 SAS AF: 0.792

Gnomad4 FIN AF: 0.787

Gnomad4 NFE AF: 0.683

Gnomad4 OTH AF: 0.761

Alfa AF: 0.726 Hom.: 14256

Bravo AF: 0.756

Asia WGS AF: 0.753 AC: 2617 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.1
DANN	Benign	0.49

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: rs13241465; hg19: chr7-33506549;