7-33196587-A-T

Variant names:

• chr7-33196587-A-T
• rs10486519
• NM_198428.3:c.442+18996A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198428.3(BBS9):​c.442+18996A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 152,084 control chromosomes in the GnomAD database, including 6,177 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 0.28 (6177 hom., cov: 33)
• Consequence: BBS9 NM_198428.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.599
• Publications: 4 publications found

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]

BBS9 Gene-Disease associations (from GenCC):

• Bardet-Biedl syndrome 9

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• ciliopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• Bardet-Biedl syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BBS9	NM_198428.3	c.442+18996A>T		intron_variant	Intron 5 of 22	ENST00000242067.11	NP_940820.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BBS9	ENST00000242067.11	c.442+18996A>T		intron_variant	Intron 5 of 22	1	NM_198428.3	ENSP00000242067.6

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42707 AN: 151966 Hom.: 6174 Cov.: 33

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.428

Gnomad AMR AF: 0.203

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.237

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.270

Gnomad MID AF: 0.293

Gnomad NFE AF: 0.320

Gnomad OTH AF: 0.276

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

GnomAD4 genome AF: 0.281 AC: 42726 AN: 152084 Hom.: 6177 Cov.: 33 AF XY: 0.275 AC XY: 20475 AN XY: 74350

African (AFR) AF: 0.251 AC: 10407 AN: 41488

American (AMR) AF: 0.203 AC: 3105 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.267 AC: 925 AN: 3470

East Asian (EAS) AF: 0.237 AC: 1226 AN: 5176

South Asian (SAS) AF: 0.289 AC: 1395 AN: 4822

European-Finnish (FIN) AF: 0.270 AC: 2853 AN: 10576

Middle Eastern (MID) AF: 0.305 AC: 89 AN: 292

European-Non Finnish (NFE) AF: 0.320 AC: 21756 AN: 67956

Other (OTH) AF: 0.274 AC: 580 AN: 2114

Alfa AF: 0.182 Hom.: 372

Bravo AF: 0.275

Asia WGS AF: 0.235 AC: 818 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	12
DANN	Benign	0.74
PhyloP100		0.60
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10486519; hg19: chr7-33236199;