NM_198428.3:c.-11-4616T>C

Variant names:

• chr7-33141626-T-C
• rs17169807
• NM_198428.3:c.-11-4616T>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.-11-4616T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0824 in 152,166 control chromosomes in the GnomAD database, including 548 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 0.082 (548 hom., cov: 32)
• Consequence: BBS9 NM_198428.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.73
• 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=-1.01).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198428.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BBS9	NM_198428.3	MANE Select	c.-11-4616T>C		intron	N/A	NP_940820.1
	BBS9	NM_001348041.4		c.-11-4616T>C		intron	N/A	NP_001334970.1
	BBS9	NM_001348036.1		c.-11-4616T>C		intron	N/A	NP_001334965.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BBS9	ENST00000242067.11	TSL:1 MANE Select	c.-11-4616T>C		intron	N/A	ENSP00000242067.6
	BBS9	ENST00000433714.5	TSL:1	n.-11-4616T>C		intron	N/A	ENSP00000412159.1
	BBS9	ENST00000671871.1		c.-11-4616T>C		intron	N/A	ENSP00000499908.1

Frequencies

GnomAD3 genomes AF: 0.0824 AC: 12524 AN: 152048 Hom.: 548 Cov.: 32

Gnomad AFR AF: 0.0747

Gnomad AMI AF: 0.0811

Gnomad AMR AF: 0.0590

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.0737

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.0819

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0881

Gnomad OTH AF: 0.0896

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

GnomAD4 genome AF: 0.0824 AC: 12531 AN: 152166 Hom.: 548 Cov.: 32 AF XY: 0.0819 AC XY: 6091 AN XY: 74410

African (AFR) AF: 0.0746 AC: 3098 AN: 41506

American (AMR) AF: 0.0589 AC: 900 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 370 AN: 3470

East Asian (EAS) AF: 0.0738 AC: 381 AN: 5160

South Asian (SAS) AF: 0.132 AC: 635 AN: 4820

European-Finnish (FIN) AF: 0.0819 AC: 869 AN: 10612

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0881 AC: 5988 AN: 67996

Other (OTH) AF: 0.0886 AC: 187 AN: 2110

Alfa AF: 0.0815 Hom.: 83

Bravo AF: 0.0821

Asia WGS AF: 0.0870 AC: 305 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.17
DANN	Benign	0.36
PhyloP100		-1.7
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: rs17169807; hg19: chr7-33181238;