rs10254116

Variant names:

• chr7-33197877-T-C
• rs10254116
• NM_198428.3:c.442+20286T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_198428.3(BBS9):​c.442+20286T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 151,710 control chromosomes in the GnomAD database, including 8,866 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 0.34 (8866 hom., cov: 31)
• Consequence: BBS9 NM_198428.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.948
• Publications: 9 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: Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp
• BBS9-related 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.456 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BBS9	NM_198428.3	MANE Select	c.442+20286T>C		intron	N/A	NP_940820.1	Q3SYG4-1
	BBS9	NM_001348041.4		c.442+20286T>C		intron	N/A	NP_001334970.1	A0A5F9ZH14
	BBS9	NM_001348036.1		c.442+20286T>C		intron	N/A	NP_001334965.1	Q3SYG4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BBS9	ENST00000242067.11	TSL:1 MANE Select	c.442+20286T>C		intron	N/A	ENSP00000242067.6	Q3SYG4-1
	BBS9	ENST00000425508.6	TSL:1	c.307+20286T>C		intron	N/A	ENSP00000405151.2	Q3SYG4-5
	BBS9	ENST00000433714.5	TSL:1	n.442+20286T>C		intron	N/A	ENSP00000412159.1	F8WCG5

Frequencies

GnomAD3 genomes AF: 0.336 AC: 50946 AN: 151594 Hom.: 8861 Cov.: 31

Gnomad AFR AF: 0.312

Gnomad AMI AF: 0.253

Gnomad AMR AF: 0.464

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.307

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.384

Gnomad MID AF: 0.295

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.348

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

GnomAD4 genome AF: 0.336 AC: 50968 AN: 151710 Hom.: 8866 Cov.: 31 AF XY: 0.342 AC XY: 25394 AN XY: 74146

African (AFR) AF: 0.312 AC: 12912 AN: 41422

American (AMR) AF: 0.465 AC: 7080 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.264 AC: 914 AN: 3468

East Asian (EAS) AF: 0.307 AC: 1589 AN: 5174

South Asian (SAS) AF: 0.229 AC: 1106 AN: 4820

European-Finnish (FIN) AF: 0.384 AC: 4045 AN: 10536

Middle Eastern (MID) AF: 0.297 AC: 85 AN: 286

European-Non Finnish (NFE) AF: 0.329 AC: 22279 AN: 67756

Other (OTH) AF: 0.345 AC: 727 AN: 2106

Alfa AF: 0.329 Hom.: 31625

Bravo AF: 0.342

Asia WGS AF: 0.265 AC: 909 AN: 3430

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	14
DANN	Benign	0.92
PhyloP100		0.95
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: rs10254116; hg19: chr7-33237489;