7-33604984-C-T

Variant names:

• chr7-33604984-C-T
• rs148654647
• ENST00000434373.3:c.1339C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The ENST00000434373.3(BBS9):​c.1339C>T​(p.Leu447Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,439,764 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: BBS9 ENST00000434373.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.379
• 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.038).
• BP7: Synonymous conserved (PhyloP=0.379 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000434373.3. 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.2632+9C>T		intron	N/A	NP_940820.1	Q3SYG4-1
	BBS9	NM_001348041.4		c.2632+9C>T		intron	N/A	NP_001334970.1	A0A5F9ZH14
	BBS9	NM_001348036.1		c.2632+9C>T		intron	N/A	NP_001334965.1	Q3SYG4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BBS9	ENST00000434373.3	TSL:1	c.1339C>T	p.Leu447Leu	synonymous	Exon 11 of 11	ENSP00000388114.1	H7BZ69
	BBS9	ENST00000242067.11	TSL:1 MANE Select	c.2632+9C>T		intron	N/A	ENSP00000242067.6	Q3SYG4-1
	BBS9	ENST00000433714.5	TSL:1	n.*1393+9C>T		intron	N/A	ENSP00000412159.1	F8WCG5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1439764 Hom.: 0 Cov.: 29 AF XY: 0.00000139 AC XY: 1 AN XY: 717764

African (AFR) AF: 0.00 AC: 0 AN: 32990

American (AMR) AF: 0.00 AC: 0 AN: 44616

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26022

East Asian (EAS) AF: 0.00 AC: 0 AN: 39500

South Asian (SAS) AF: 0.00 AC: 0 AN: 85758

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53382

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5712

European-Non Finnish (NFE) AF: 0.00000183 AC: 2 AN: 1092094

Other (OTH) AF: 0.00 AC: 0 AN: 59690

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	7.2
DANN	Benign	0.69
PhyloP100		0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs148654647; hg19: chr7-33644596;