chr7-33345650-G-T

Position:

• chr7-33345650-G-T

Variant summary

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

The NM_198428.3(BBS9):​c.1329+1016G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 151,954 control chromosomes in the GnomAD database, including 15,576 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 0.45 (15576 hom., cov: 32)
• Consequence: BBS9 NM_198428.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.177

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=-0.56).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BBS9	NM_198428.3	c.1329+1016G>T		intron_variant		ENST00000242067.11	NP_940820.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BBS9	ENST00000242067.11	c.1329+1016G>T		intron_variant		1	NM_198428.3	ENSP00000242067.6

Frequencies

GnomAD3 genomes AF: 0.449 AC: 68187 AN: 151836 Hom.: 15572 Cov.: 32

Gnomad AFR AF: 0.374

Gnomad AMI AF: 0.455

Gnomad AMR AF: 0.531

Gnomad ASJ AF: 0.523

Gnomad EAS AF: 0.458

Gnomad SAS AF: 0.465

Gnomad FIN AF: 0.473

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.466

Gnomad OTH AF: 0.474

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

GnomAD4 genome AF: 0.449 AC: 68228 AN: 151954 Hom.: 15576 Cov.: 32 AF XY: 0.453 AC XY: 33649 AN XY: 74252

Gnomad4 AFR AF: 0.374

Gnomad4 AMR AF: 0.532

Gnomad4 ASJ AF: 0.523

Gnomad4 EAS AF: 0.459

Gnomad4 SAS AF: 0.464

Gnomad4 FIN AF: 0.473

Gnomad4 NFE AF: 0.466

Gnomad4 OTH AF: 0.473

Alfa AF: 0.467 Hom.: 27674

Bravo AF: 0.452

Asia WGS AF: 0.463 AC: 1611 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	8.3
DANN	Benign	0.55

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: rs3884597; hg19: chr7-33385262;