NM_198428.3:c.442+21631A>G

Variant names:

• chr7-33199222-A-G
• rs10272438
• NM_198428.3:c.442+21631A>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.442+21631A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 151,842 control chromosomes in the GnomAD database, including 3,525 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 0.19 (3525 hom., cov: 32)
• Consequence: BBS9 NM_198428.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.290
• Publications: 19 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.328 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BBS9	NM_198428.3	c.442+21631A>G		intron_variant	Intron 5 of 22	ENST00000242067.11	NP_940820.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BBS9	ENST00000242067.11	c.442+21631A>G		intron_variant	Intron 5 of 22	1	NM_198428.3	ENSP00000242067.6

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28339 AN: 151724 Hom.: 3520 Cov.: 32

Gnomad AFR AF: 0.0494

Gnomad AMI AF: 0.217

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.0333

Gnomad SAS AF: 0.0882

Gnomad FIN AF: 0.261

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.215

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

GnomAD4 genome AF: 0.187 AC: 28352 AN: 151842 Hom.: 3525 Cov.: 32 AF XY: 0.191 AC XY: 14151 AN XY: 74204

African (AFR) AF: 0.0493 AC: 2047 AN: 41544

American (AMR) AF: 0.336 AC: 5127 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 721 AN: 3454

East Asian (EAS) AF: 0.0336 AC: 174 AN: 5178

South Asian (SAS) AF: 0.0880 AC: 424 AN: 4816

European-Finnish (FIN) AF: 0.261 AC: 2756 AN: 10540

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.242 AC: 16394 AN: 67734

Other (OTH) AF: 0.213 AC: 447 AN: 2100

Alfa AF: 0.211 Hom.: 608

Bravo AF: 0.188

Asia WGS AF: 0.0640 AC: 224 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.47
DANN	Benign	0.78
PhyloP100		0.29
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: rs10272438; hg19: chr7-33238834;