rs35195153

Variant names:

• chr7-33336453-A-G
• rs35195153
• NM_198428.3:c.1029A>G

Your query was ambiguous. Multiple possible variants found:

• chr7-33336453-A-G
• chr7-33336453-A-C

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.1029A>G​(p.Gly343Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00806 in 1,613,376 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 (200 hom., cov: 32)
  • Exomes 𝑓: 0.0060 (252 hom.)
• Consequence: BBS9 NM_198428.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.645
• 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 7-33336453-A-G is Benign according to our data. Variant chr7-33336453-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 263112.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.645 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0899 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.1029A>G	p.Gly343Gly	synonymous	Exon 10 of 23	NP_940820.1	Q3SYG4-1
	BBS9	NM_001348041.4		c.1029A>G	p.Gly343Gly	synonymous	Exon 10 of 23	NP_001334970.1	A0A5F9ZH14
	BBS9	NM_001348036.1		c.1029A>G	p.Gly343Gly	synonymous	Exon 10 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.1029A>G	p.Gly343Gly	synonymous	Exon 10 of 23	ENSP00000242067.6	Q3SYG4-1
	BBS9	ENST00000433714.5	TSL:1	n.1029A>G		non_coding_transcript_exon	Exon 10 of 24	ENSP00000412159.1	F8WCG5
	BBS9	ENST00000942912.1		c.1155A>G	p.Gly385Gly	synonymous	Exon 11 of 24	ENSP00000612971.1

Frequencies

GnomAD3 genomes AF: 0.0281 AC: 4277 AN: 152158 Hom.: 199 Cov.: 32

Gnomad AFR AF: 0.0921

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00988

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0356

Gnomad FIN AF: 0.000282

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00138

Gnomad OTH AF: 0.0182

GnomAD2 exomes AF: 0.0121 AC: 3048 AN: 251054 AF XY: 0.0120

Gnomad AFR exome AF: 0.0965

Gnomad AMR exome AF: 0.00565

Gnomad ASJ exome AF: 0.000695

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.00159

Gnomad OTH exome AF: 0.00441

GnomAD4 exome AF: 0.00596 AC: 8706 AN: 1461100 Hom.: 252 Cov.: 30 AF XY: 0.00657 AC XY: 4777 AN XY: 726894

African (AFR) AF: 0.101 AC: 3368 AN: 33438

American (AMR) AF: 0.00544 AC: 243 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.000498 AC: 13 AN: 26126

East Asian (EAS) AF: 0.000277 AC: 11 AN: 39658

South Asian (SAS) AF: 0.0333 AC: 2869 AN: 86194

European-Finnish (FIN) AF: 0.000206 AC: 11 AN: 53398

Middle Eastern (MID) AF: 0.00643 AC: 37 AN: 5752

European-Non Finnish (NFE) AF: 0.00137 AC: 1528 AN: 1111460

Other (OTH) AF: 0.0104 AC: 626 AN: 60366

GnomAD4 genome AF: 0.0282 AC: 4298 AN: 152276 Hom.: 200 Cov.: 32 AF XY: 0.0278 AC XY: 2073 AN XY: 74486

African (AFR) AF: 0.0923 AC: 3834 AN: 41536

American (AMR) AF: 0.00987 AC: 151 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.0359 AC: 173 AN: 4824

European-Finnish (FIN) AF: 0.000282 AC: 3 AN: 10622

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

European-Non Finnish (NFE) AF: 0.00138 AC: 94 AN: 68026

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

Alfa AF: 0.0130 Hom.: 72

Bravo AF: 0.0315

Asia WGS AF: 0.0230 AC: 79 AN: 3478

EpiCase AF: 0.000709

EpiControl AF: 0.00119

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	5.3
DANN	Benign	0.60
PhyloP100		-0.65
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: rs35195153; hg19: chr7-33376065; COSMIC: COSV107282834;