rs187651906

Variant names:

• chr7-33264407-A-G
• rs187651906
• NM_198428.3:c.702+33A>G

Your query was ambiguous. Multiple possible variants found:

• chr7-33264407-A-G
• chr7-33264407-A-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 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: G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• 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 -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BBS9	NM_198428.3	c.702+33A>G		intron_variant	Intron 7 of 22	ENST00000242067.11	NP_940820.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BBS9	ENST00000242067.11	c.702+33A>G		intron_variant	Intron 7 of 22	1	NM_198428.3	ENSP00000242067.6

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

GnomAD2 exomes AF: 0.00124 AC: 279 AN: 224244 AF XY: 0.000969

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 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

African (AFR) AF: 0.0107 AC: 267 AN: 24860

American (AMR) AF: 0.00250 AC: 98 AN: 39158

Ashkenazi Jewish (ASJ) AF: 0.000492 AC: 11 AN: 22364

East Asian (EAS) AF: 0.00 AC: 0 AN: 37018

South Asian (SAS) AF: 0.000104 AC: 7 AN: 67438

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50268

Middle Eastern (MID) AF: 0.00357 AC: 12 AN: 3360

European-Non Finnish (NFE) AF: 0.000327 AC: 256 AN: 782104

Other (OTH) AF: 0.00152 AC: 71 AN: 46590

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

African (AFR) AF: 0.0109 AC: 453 AN: 41544

American (AMR) AF: 0.00137 AC: 21 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000456 AC: 31 AN: 67946

Other (OTH) AF: 0.00379 AC: 8 AN: 2112

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

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.19
DANN	Benign	0.69
PhyloP100		-0.41
Mutation Taster		=100/0	polymorphism

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: rs187651906; hg19: chr7-33304019;