rs11981364

Variant names:

• chr7-33340986-G-T
• rs11981364
• NM_198428.3:c.1275+13G>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_198428.3(BBS9):​c.1275+13G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 1,606,276 control chromosomes in the GnomAD database, including 65,673 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.26 (5526 hom., cov: 31)
  • Exomes 𝑓: 0.28 (60147 hom.)
• Consequence: BBS9 NM_198428.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.538
• Publications: 8 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 7-33340986-G-T is Benign according to our data. Variant chr7-33340986-G-T is described in ClinVar as Benign. ClinVar VariationId is 263114.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.3 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.1275+13G>T		intron	N/A	NP_940820.1	Q3SYG4-1
	BBS9	NM_001348041.4		c.1275+13G>T		intron	N/A	NP_001334970.1	A0A5F9ZH14
	BBS9	NM_001348036.1		c.1275+13G>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.1275+13G>T		intron	N/A	ENSP00000242067.6	Q3SYG4-1
	BBS9	ENST00000433714.5	TSL:1	n.1275+13G>T		intron	N/A	ENSP00000412159.1	F8WCG5
	BBS9	ENST00000942912.1		c.1401+13G>T		intron	N/A	ENSP00000612971.1

Frequencies

GnomAD3 genomes AF: 0.264 AC: 40100 AN: 151864 Hom.: 5525 Cov.: 31

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.442

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.0749

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.242

Gnomad NFE AF: 0.304

Gnomad OTH AF: 0.250

GnomAD2 exomes AF: 0.240 AC: 60175 AN: 250864 AF XY: 0.243

Gnomad AFR exome AF: 0.241

Gnomad AMR exome AF: 0.141

Gnomad ASJ exome AF: 0.251

Gnomad EAS exome AF: 0.0714

Gnomad FIN exome AF: 0.273

Gnomad NFE exome AF: 0.297

Gnomad OTH exome AF: 0.260

GnomAD4 exome AF: 0.281 AC: 409159 AN: 1454294 Hom.: 60147 Cov.: 29 AF XY: 0.279 AC XY: 202325 AN XY: 724008

African (AFR) AF: 0.248 AC: 8270 AN: 33342

American (AMR) AF: 0.150 AC: 6683 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.249 AC: 6492 AN: 26082

East Asian (EAS) AF: 0.0514 AC: 2035 AN: 39624

South Asian (SAS) AF: 0.211 AC: 18205 AN: 86082

European-Finnish (FIN) AF: 0.276 AC: 14702 AN: 53214

Middle Eastern (MID) AF: 0.266 AC: 1527 AN: 5750

European-Non Finnish (NFE) AF: 0.303 AC: 334874 AN: 1105398

Other (OTH) AF: 0.272 AC: 16371 AN: 60114

GnomAD4 genome AF: 0.264 AC: 40106 AN: 151982 Hom.: 5526 Cov.: 31 AF XY: 0.258 AC XY: 19182 AN XY: 74286

African (AFR) AF: 0.246 AC: 10192 AN: 41474

American (AMR) AF: 0.208 AC: 3176 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.247 AC: 857 AN: 3468

East Asian (EAS) AF: 0.0749 AC: 387 AN: 5168

South Asian (SAS) AF: 0.215 AC: 1034 AN: 4816

European-Finnish (FIN) AF: 0.268 AC: 2823 AN: 10540

Middle Eastern (MID) AF: 0.243 AC: 71 AN: 292

European-Non Finnish (NFE) AF: 0.304 AC: 20641 AN: 67936

Other (OTH) AF: 0.247 AC: 522 AN: 2112

Alfa AF: 0.281 Hom.: 1130

Bravo AF: 0.258

Asia WGS AF: 0.139 AC: 485 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	1	Bardet-Biedl syndrome (1)
-	-	1	Bardet-Biedl syndrome 9 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	7.2
DANN	Benign	0.79
PhyloP100		-0.54
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: rs11981364; hg19: chr7-33380598;