chr7-33466937-T-G

Variant names:

• chr7-33466937-T-G
• rs13241465
• NM_198428.3:c.2116-38526T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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=-0.91).
• 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 rank	MANE	Protein	UniProt
BBS9	NM_198428.3	c.2116-38526T>G		intron_variant	Intron 19 of 22	ENST00000242067.11	NP_940820.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BBS9	ENST00000242067.11	c.2116-38526T>G		intron_variant	Intron 19 of 22	1	NM_198428.3	ENSP00000242067.6

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

African (AFR) AF: 0.853 AC: 35341 AN: 41452

American (AMR) AF: 0.789 AC: 12044 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.653 AC: 2266 AN: 3468

East Asian (EAS) AF: 0.722 AC: 3698 AN: 5124

South Asian (SAS) AF: 0.792 AC: 3815 AN: 4816

European-Finnish (FIN) AF: 0.787 AC: 8298 AN: 10550

Middle Eastern (MID) AF: 0.769 AC: 226 AN: 294

European-Non Finnish (NFE) AF: 0.683 AC: 46401 AN: 67888

Other (OTH) AF: 0.761 AC: 1605 AN: 2110

Alfa AF: 0.725 Hom.: 17296

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
PhyloP100		0.10
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: rs13241465; hg19: chr7-33506549;