rs6964382

Variant names:

• chr7-33344589-C-T
• rs6964382
• NM_198428.3:c.1284C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_198428.3(BBS9):​c.1284C>T​(p.Thr428Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00729 in 1,613,828 control chromosomes in the GnomAD database, including 452 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.028 (199 hom., cov: 31)
  • Exomes 𝑓: 0.0051 (253 hom.)
• Consequence: BBS9 NM_198428.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.265
• Publications: 3 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 7-33344589-C-T is Benign according to our data. Variant chr7-33344589-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 263116.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.265 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0909 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.1284C>T	p.Thr428Thr	synonymous	Exon 12 of 23	NP_940820.1	Q3SYG4-1
	BBS9	NM_001348041.4		c.1284C>T	p.Thr428Thr	synonymous	Exon 12 of 23	NP_001334970.1	A0A5F9ZH14
	BBS9	NM_001348036.1		c.1284C>T	p.Thr428Thr	synonymous	Exon 12 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.1284C>T	p.Thr428Thr	synonymous	Exon 12 of 23	ENSP00000242067.6	Q3SYG4-1
	BBS9	ENST00000433714.5	TSL:1	n.1284C>T		non_coding_transcript_exon	Exon 12 of 24	ENSP00000412159.1	F8WCG5
	BBS9	ENST00000942912.1		c.1410C>T	p.Thr470Thr	synonymous	Exon 13 of 24	ENSP00000612971.1

Frequencies

GnomAD3 genomes AF: 0.0278 AC: 4232 AN: 152006 Hom.: 197 Cov.: 31

Gnomad AFR AF: 0.0928

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0101

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0355

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000382

Gnomad OTH AF: 0.0182

GnomAD2 exomes AF: 0.0115 AC: 2903 AN: 251490 AF XY: 0.0114

Gnomad AFR exome AF: 0.0968

Gnomad AMR exome AF: 0.00575

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000290

Gnomad OTH exome AF: 0.00358

GnomAD4 exome AF: 0.00513 AC: 7496 AN: 1461704 Hom.: 253 Cov.: 31 AF XY: 0.00577 AC XY: 4194 AN XY: 727150

African (AFR) AF: 0.101 AC: 3381 AN: 33452

American (AMR) AF: 0.00557 AC: 249 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.000302 AC: 12 AN: 39676

South Asian (SAS) AF: 0.0333 AC: 2876 AN: 86240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00745 AC: 43 AN: 5768

European-Non Finnish (NFE) AF: 0.000305 AC: 339 AN: 1111918

Other (OTH) AF: 0.00987 AC: 596 AN: 60384

GnomAD4 genome AF: 0.0280 AC: 4264 AN: 152124 Hom.: 199 Cov.: 31 AF XY: 0.0279 AC XY: 2073 AN XY: 74384

African (AFR) AF: 0.0933 AC: 3870 AN: 41476

American (AMR) AF: 0.0101 AC: 154 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5178

South Asian (SAS) AF: 0.0357 AC: 172 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10588

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

European-Non Finnish (NFE) AF: 0.000382 AC: 26 AN: 67990

Other (OTH) AF: 0.0180 AC: 38 AN: 2112

Alfa AF: 0.0155 Hom.: 217

Bravo AF: 0.0313

Asia WGS AF: 0.0250 AC: 85 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000296

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	1	Bardet-Biedl syndrome (1)
-	-	1	Bardet-Biedl syndrome 9 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	6.6
DANN	Benign	0.47
PhyloP100		0.27
PromoterAI		-0.029	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs6964382; hg19: chr7-33384201; COSMIC: COSV107282835; COSMIC: COSV107282835;