7-33196686-T-C

Variant names:

• chr7-33196686-T-C
• rs964707
• NM_198428.3:c.442+19095T>C

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+19095T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.808 in 152,122 control chromosomes in the GnomAD database, including 49,883 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 0.81 (49883 hom., cov: 31)
• Consequence: BBS9 NM_198428.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.158
• Publications: 3 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=-0.71).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.848 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BBS9	NM_198428.3	c.442+19095T>C		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+19095T>C		intron_variant	Intron 5 of 22	1	NM_198428.3	ENSP00000242067.6

Frequencies

GnomAD3 genomes AF: 0.808 AC: 122849 AN: 152004 Hom.: 49843 Cov.: 31

Gnomad AFR AF: 0.740

Gnomad AMI AF: 0.766

Gnomad AMR AF: 0.860

Gnomad ASJ AF: 0.741

Gnomad EAS AF: 0.702

Gnomad SAS AF: 0.791

Gnomad FIN AF: 0.864

Gnomad MID AF: 0.823

Gnomad NFE AF: 0.842

Gnomad OTH AF: 0.825

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

GnomAD4 genome AF: 0.808 AC: 122948 AN: 152122 Hom.: 49883 Cov.: 31 AF XY: 0.812 AC XY: 60359 AN XY: 74378

African (AFR) AF: 0.740 AC: 30693 AN: 41478

American (AMR) AF: 0.860 AC: 13152 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.741 AC: 2571 AN: 3468

East Asian (EAS) AF: 0.701 AC: 3625 AN: 5170

South Asian (SAS) AF: 0.793 AC: 3820 AN: 4820

European-Finnish (FIN) AF: 0.864 AC: 9160 AN: 10604

Middle Eastern (MID) AF: 0.837 AC: 246 AN: 294

European-Non Finnish (NFE) AF: 0.842 AC: 57244 AN: 67978

Other (OTH) AF: 0.824 AC: 1740 AN: 2112

Alfa AF: 0.809 Hom.: 12702

Bravo AF: 0.803

Asia WGS AF: 0.729 AC: 2535 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	13
DANN	Benign	0.51
PhyloP100		-0.16
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: rs964707; hg19: chr7-33236298;