chr7-33336453-A-G

Position:

• chr7-33336453-A-G

Variant summary

Our verdict is Benign. Variant got -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:5
• Conservation: PhyloP100: -0.645

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BBS9	NM_198428.3	c.1029A>G	p.Gly343Gly	synonymous_variant	10/23	ENST00000242067.11	NP_940820.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BBS9	ENST00000242067.11	c.1029A>G	p.Gly343Gly	synonymous_variant	10/23	1	NM_198428.3	ENSP00000242067.6

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

GnomAD3 exomes AF: 0.0121 AC: 3048 AN: 251054 Hom.: 107 AF XY: 0.0120 AC XY: 1635 AN XY: 135688

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 SAS exome AF: 0.0350

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

Gnomad4 AFR exome AF: 0.101

Gnomad4 AMR exome AF: 0.00544

Gnomad4 ASJ exome AF: 0.000498

Gnomad4 EAS exome AF: 0.000277

Gnomad4 SAS exome AF: 0.0333

Gnomad4 FIN exome AF: 0.000206

Gnomad4 NFE exome AF: 0.00137

Gnomad4 OTH exome AF: 0.0104

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

Gnomad4 AFR AF: 0.0923

Gnomad4 AMR AF: 0.00987

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0359

Gnomad4 FIN AF: 0.000282

Gnomad4 NFE AF: 0.00138

Gnomad4 OTH AF: 0.0180

Alfa AF: 0.0127 Hom.: 59

Bravo AF: 0.0315

Asia WGS AF: 0.0230 AC: 79 AN: 3478

EpiCase AF: 0.000709

EpiControl AF: 0.00119

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 10, 2021	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Bardet-Biedl syndrome 9 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Bardet-Biedl syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	5.3
DANN	Benign	0.60

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

Publications

LitVar

Other links and lift over

dbSNP: rs35195153; hg19: chr7-33376065;