7-33876587-A-G

Variant names:

• chr7-33876587-A-G
• rs10486621
• ENST00000672453.1:n.2704-465A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000672453.1(BBS9):​n.2704-465A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0111 in 152,304 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.011 (11 hom., cov: 32)
• Consequence: BBS9 ENST00000672453.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.759
• Publications: 1 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

LOC124901613 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0111 (1691/152304) while in subpopulation NFE AF = 0.0153 (1040/68012). AF 95% confidence interval is 0.0145. There are 11 homozygotes in GnomAd4. There are 786 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC124901613	XR_007060282.1	n.115-465A>G		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BBS9	ENST00000672453.1	n.2704-465A>G		intron_variant	Intron 22 of 22

Frequencies

GnomAD3 genomes AF: 0.0111 AC: 1693 AN: 152186 Hom.: 11 Cov.: 32

Gnomad AFR AF: 0.00306

Gnomad AMI AF: 0.0910

Gnomad AMR AF: 0.0148

Gnomad ASJ AF: 0.0239

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00849

Gnomad FIN AF: 0.00621

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0153

Gnomad OTH AF: 0.0110

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0111 AC: 1691 AN: 152304 Hom.: 11 Cov.: 32 AF XY: 0.0106 AC XY: 786 AN XY: 74470

African (AFR) AF: 0.00308 AC: 128 AN: 41580

American (AMR) AF: 0.0148 AC: 226 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0239 AC: 83 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00870 AC: 42 AN: 4828

European-Finnish (FIN) AF: 0.00621 AC: 66 AN: 10624

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

European-Non Finnish (NFE) AF: 0.0153 AC: 1040 AN: 68012

Other (OTH) AF: 0.0104 AC: 22 AN: 2114

Alfa AF: 0.0121 Hom.: 2

Bravo AF: 0.0116

Asia WGS AF: 0.00549 AC: 20 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	16
DANN	Benign	0.73
PhyloP100		0.76

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10486621; hg19: chr7-33916199;