7-33295780-C-T

Variant names:

• chr7-33295780-C-T
• rs10486526
• NM_198428.3:c.1016+21824C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_198428.3(BBS9):​c.1016+21824C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0199 in 152,050 control chromosomes in the GnomAD database, including 52 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 0.020 (52 hom., cov: 32)
• Consequence: BBS9 NM_198428.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39
• Publications: 0 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0199 (3028/152050) while in subpopulation NFE AF = 0.0302 (2049/67900). AF 95% confidence interval is 0.0291. There are 52 homozygotes in GnomAd4. There are 1475 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 52 AR gene

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.1016+21824C>T		intron	N/A	NP_940820.1	Q3SYG4-1
	BBS9	NM_001348041.4		c.1016+21824C>T		intron	N/A	NP_001334970.1	A0A5F9ZH14
	BBS9	NM_001348036.1		c.1016+21824C>T		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.1016+21824C>T		intron	N/A	ENSP00000242067.6	Q3SYG4-1
	BBS9	ENST00000425508.6	TSL:1	c.882-18480C>T		intron	N/A	ENSP00000405151.2	Q3SYG4-5
	BBS9	ENST00000433714.5	TSL:1	n.1016+21824C>T		intron	N/A	ENSP00000412159.1	F8WCG5

Frequencies

GnomAD3 genomes AF: 0.0199 AC: 3027 AN: 151932 Hom.: 52 Cov.: 32

Gnomad AFR AF: 0.00524

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.0138

Gnomad ASJ AF: 0.0228

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0133

Gnomad FIN AF: 0.0326

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.0302

Gnomad OTH AF: 0.0173

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

GnomAD4 genome AF: 0.0199 AC: 3028 AN: 152050 Hom.: 52 Cov.: 32 AF XY: 0.0198 AC XY: 1475 AN XY: 74342

African (AFR) AF: 0.00523 AC: 217 AN: 41528

American (AMR) AF: 0.0138 AC: 210 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.0228 AC: 79 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5180

South Asian (SAS) AF: 0.0137 AC: 66 AN: 4818

European-Finnish (FIN) AF: 0.0326 AC: 345 AN: 10572

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0302 AC: 2049 AN: 67900

Other (OTH) AF: 0.0166 AC: 35 AN: 2108

Alfa AF: 0.00575 Hom.: 2

Bravo AF: 0.0181

Asia WGS AF: 0.00494 AC: 18 AN: 3456

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.27
DANN	Benign	0.22
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism

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: rs10486526; hg19: chr7-33335392;