rs4723261

Variant names:

• chr7-33148184-T-A
• rs4723261
• NM_198428.3:c.112+1820T>A

Your query was ambiguous. Multiple possible variants found:

• chr7-33148184-T-A
• chr7-33148184-T-C
• chr7-33148184-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198428.3(BBS9):​c.112+1820T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.877 in 152,238 control chromosomes in the GnomAD database, including 58,819 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 0.88 (58819 hom., cov: 32)
• Consequence: BBS9 NM_198428.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.306
• Publications: 4 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.963 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BBS9	NM_198428.3	c.112+1820T>A		intron_variant	Intron 2 of 22	ENST00000242067.11	NP_940820.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BBS9	ENST00000242067.11	c.112+1820T>A		intron_variant	Intron 2 of 22	1	NM_198428.3	ENSP00000242067.6

Frequencies

GnomAD3 genomes AF: 0.877 AC: 133372 AN: 152120 Hom.: 58752 Cov.: 32

Gnomad AFR AF: 0.971

Gnomad AMI AF: 0.765

Gnomad AMR AF: 0.889

Gnomad ASJ AF: 0.744

Gnomad EAS AF: 0.709

Gnomad SAS AF: 0.833

Gnomad FIN AF: 0.863

Gnomad MID AF: 0.832

Gnomad NFE AF: 0.844

Gnomad OTH AF: 0.872

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

GnomAD4 genome AF: 0.877 AC: 133500 AN: 152238 Hom.: 58819 Cov.: 32 AF XY: 0.877 AC XY: 65296 AN XY: 74416

African (AFR) AF: 0.971 AC: 40337 AN: 41556

American (AMR) AF: 0.889 AC: 13601 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.744 AC: 2580 AN: 3470

East Asian (EAS) AF: 0.708 AC: 3658 AN: 5164

South Asian (SAS) AF: 0.834 AC: 4020 AN: 4820

European-Finnish (FIN) AF: 0.863 AC: 9142 AN: 10592

Middle Eastern (MID) AF: 0.847 AC: 249 AN: 294

European-Non Finnish (NFE) AF: 0.844 AC: 57374 AN: 68018

Other (OTH) AF: 0.870 AC: 1841 AN: 2116

Alfa AF: 0.830 Hom.: 3014

Bravo AF: 0.881

Asia WGS AF: 0.772 AC: 2685 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.1
DANN	Benign	0.83
PhyloP100		-0.31
Mutation Taster		=100/0	polymorphism (auto)

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: rs4723261; hg19: chr7-33187796;