7-33216427-A-C

Position:

• chr7-33216427-A-C

Variant summary

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

The NM_198428.3(BBS9):​c.442+38836A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 152,124 control chromosomes in the GnomAD database, including 6,164 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 0.27 (6164 hom., cov: 33)
• Consequence: BBS9 NM_198428.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.565

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.405 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BBS9	NM_198428.3	c.442+38836A>C		intron_variant		ENST00000242067.11	NP_940820.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BBS9	ENST00000242067.11	c.442+38836A>C		intron_variant		1	NM_198428.3	ENSP00000242067	P3

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40752 AN: 152006 Hom.: 6159 Cov.: 33

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.412

Gnomad ASJ AF: 0.245

Gnomad EAS AF: 0.0339

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.333

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.290

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

GnomAD4 genome AF: 0.268 AC: 40765 AN: 152124 Hom.: 6164 Cov.: 33 AF XY: 0.273 AC XY: 20269 AN XY: 74366

Gnomad4 AFR AF: 0.167

Gnomad4 AMR AF: 0.413

Gnomad4 ASJ AF: 0.245

Gnomad4 EAS AF: 0.0342

Gnomad4 SAS AF: 0.216

Gnomad4 FIN AF: 0.333

Gnomad4 NFE AF: 0.309

Gnomad4 OTH AF: 0.287

Alfa AF: 0.311 Hom.: 7073

Bravo AF: 0.270

Asia WGS AF: 0.135 AC: 470 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.6
DANN	Benign	0.78

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: rs10262453; hg19: chr7-33256039;