rs140169161

Variant names:

• chr7-33264293-C-T
• rs140169161
• NM_198428.3:c.621C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP6_Very_Strong BP7

The NM_198428.3(BBS9):​c.621C>T​(p.Tyr207Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000265 in 1,527,642 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00028 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00026 (1 hom.)
• Consequence: BBS9 NM_198428.3 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.27
• 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 7-33264293-C-T is Benign according to our data. Variant chr7-33264293-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 434500.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.27 with no splicing effect.

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.621C>T	p.Tyr207Tyr	synonymous	Exon 7 of 23	NP_940820.1	Q3SYG4-1
	BBS9	NM_001348041.4		c.621C>T	p.Tyr207Tyr	synonymous	Exon 7 of 23	NP_001334970.1	A0A5F9ZH14
	BBS9	NM_001348036.1		c.621C>T	p.Tyr207Tyr	synonymous	Exon 7 of 23	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.621C>T	p.Tyr207Tyr	synonymous	Exon 7 of 23	ENSP00000242067.6	Q3SYG4-1
	BBS9	ENST00000425508.6	TSL:1	c.486C>T	p.Tyr162Tyr	synonymous	Exon 6 of 9	ENSP00000405151.2	Q3SYG4-5
	BBS9	ENST00000433714.5	TSL:1	n.621C>T		non_coding_transcript_exon	Exon 7 of 24	ENSP00000412159.1	F8WCG5

Frequencies

GnomAD3 genomes AF: 0.000277 AC: 42 AN: 151534 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000328

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000472

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000176 AC: 40 AN: 226756 AF XY: 0.000154

Gnomad AFR exome AF: 0.000137

Gnomad AMR exome AF: 0.000373

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000238

Gnomad OTH exome AF: 0.000376

GnomAD4 exome AF: 0.000264 AC: 363 AN: 1375990 Hom.: 1 Cov.: 27 AF XY: 0.000265 AC XY: 181 AN XY: 681900

African (AFR) AF: 0.0000964 AC: 3 AN: 31106

American (AMR) AF: 0.000359 AC: 14 AN: 39026

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24002

East Asian (EAS) AF: 0.00 AC: 0 AN: 37862

South Asian (SAS) AF: 0.00 AC: 0 AN: 67438

European-Finnish (FIN) AF: 0.0000401 AC: 2 AN: 49824

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4244

European-Non Finnish (NFE) AF: 0.000311 AC: 332 AN: 1066196

Other (OTH) AF: 0.000213 AC: 12 AN: 56292

GnomAD4 genome AF: 0.000277 AC: 42 AN: 151652 Hom.: 0 Cov.: 32 AF XY: 0.000229 AC XY: 17 AN XY: 74116

African (AFR) AF: 0.000121 AC: 5 AN: 41380

American (AMR) AF: 0.000328 AC: 5 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4796

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10432

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000472 AC: 32 AN: 67848

Other (OTH) AF: 0.00 AC: 0 AN: 2096

Alfa AF: 0.000182 Hom.: 1

Bravo AF: 0.000295

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Bardet-Biedl syndrome (1)
-	-	1	Bardet-Biedl syndrome 9 (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	8.4
DANN	Benign	0.48
PhyloP100		1.3

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: rs140169161; hg19: chr7-33303905;