rs187651906

chr7-33264407-A-Gchr7-33264407-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_198428.3(BBS9):c.702+33A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00101 in 1,225,352 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0034 (4 hom., cov: 32)
  • Exomes 𝑓: 0.00067 (3 hom.)
• Consequence: BBS9 NM_198428.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.408

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 7-33264407-A-G is Benign according to our data. Variant chr7-33264407-A-G is described in ClinVar as [Benign]. Clinvar id is 263131.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00338 (515/152192) while in subpopulation AFR AF= 0.0109 (453/41544). AF 95% confidence interval is 0.0101. There are 4 homozygotes in gnomad4. There are 238 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BBS9	NM_198428.3	c.702+33A>G		intron_variant		ENST00000242067.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BBS9	ENST00000242067.11	c.702+33A>G		intron_variant		1	NM_198428.3	P3

Frequencies

GnomAD3 genomes AF: 0.00338 AC: 514 AN: 152074 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.0109

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00137

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000456

Gnomad OTH AF: 0.00383

GnomAD3 exomes AF: 0.00124 AC: 279 AN: 224244 Hom.: 1 AF XY: 0.000969 AC XY: 119 AN XY: 122768

Gnomad AFR exome AF: 0.0101

Gnomad AMR exome AF: 0.00236

Gnomad ASJ exome AF: 0.000340

Gnomad EAS exome AF: 0.000124

Gnomad SAS exome AF: 0.000113

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000494

Gnomad OTH exome AF: 0.00169

GnomAD4 exome AF: 0.000673 AC: 722 AN: 1073160 Hom.: 3 Cov.: 14 AF XY: 0.000650 AC XY: 357 AN XY: 548818

Gnomad4 AFR exome AF: 0.0107

Gnomad4 AMR exome AF: 0.00250

Gnomad4 ASJ exome AF: 0.000492

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000104

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000327

Gnomad4 OTH exome AF: 0.00152

GnomAD4 genome AF: 0.00338 AC: 515 AN: 152192 Hom.: 4 Cov.: 32 AF XY: 0.00320 AC XY: 238 AN XY: 74404

Gnomad4 AFR AF: 0.0109

Gnomad4 AMR AF: 0.00137

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000456

Gnomad4 OTH AF: 0.00379

Alfa AF: 0.00205 Hom.: 0

Bravo AF: 0.00405

Asia WGS AF: 0.00145 AC: 5 AN: 3466

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.19
Dann	Benign	0.69

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

Publications

LitVar

Other links and lift over

dbSNP: rs187651906; hg19: chr7-33304019;