rs4236337

Variant names:

• chr7-33467294-C-A
• rs4236337
• NM_198428.3:c.2116-38169C>A

Your query was ambiguous. Multiple possible variants found:

• chr7-33467294-C-A
• chr7-33467294-C-G
• chr7-33467294-C-T

Variant summary

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

The NM_198428.3(BBS9):​c.2116-38169C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.751 in 151,916 control chromosomes in the GnomAD database, including 43,230 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 0.75 (43230 hom., cov: 30)
• Consequence: BBS9 NM_198428.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.170
• Publications: 5 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=-0.63).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.847 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BBS9	NM_198428.3	c.2116-38169C>A		intron_variant	Intron 19 of 22	ENST00000242067.11	NP_940820.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BBS9	ENST00000242067.11	c.2116-38169C>A		intron_variant	Intron 19 of 22	1	NM_198428.3	ENSP00000242067.6

Frequencies

GnomAD3 genomes AF: 0.750 AC: 113895 AN: 151798 Hom.: 43165 Cov.: 30

Gnomad AFR AF: 0.855

Gnomad AMI AF: 0.538

Gnomad AMR AF: 0.788

Gnomad ASJ AF: 0.650

Gnomad EAS AF: 0.722

Gnomad SAS AF: 0.790

Gnomad FIN AF: 0.786

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.680

Gnomad OTH AF: 0.760

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

GnomAD4 genome AF: 0.751 AC: 114019 AN: 151916 Hom.: 43230 Cov.: 30 AF XY: 0.759 AC XY: 56349 AN XY: 74280

African (AFR) AF: 0.855 AC: 35427 AN: 41442

American (AMR) AF: 0.788 AC: 12018 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.650 AC: 2254 AN: 3468

East Asian (EAS) AF: 0.721 AC: 3706 AN: 5138

South Asian (SAS) AF: 0.791 AC: 3810 AN: 4816

European-Finnish (FIN) AF: 0.786 AC: 8319 AN: 10588

Middle Eastern (MID) AF: 0.769 AC: 226 AN: 294

European-Non Finnish (NFE) AF: 0.680 AC: 46174 AN: 67914

Other (OTH) AF: 0.759 AC: 1599 AN: 2108

Alfa AF: 0.700 Hom.: 13802

Bravo AF: 0.755

Asia WGS AF: 0.752 AC: 2614 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	6.6
DANN	Benign	0.84
PhyloP100		-0.17
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: rs4236337; hg19: chr7-33506906;