NM_198428.3:c.1016+6873C>T

Variant names:

• chr7-33280829-C-T
• rs10486525
• NM_198428.3:c.1016+6873C>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.1016+6873C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 149,778 control chromosomes in the GnomAD database, including 1,131 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 0.11 (1131 hom., cov: 31)
• Consequence: BBS9 NM_198428.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.163
• Publications: 3 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BBS9	NM_198428.3	c.1016+6873C>T		intron_variant	Intron 9 of 22	ENST00000242067.11	NP_940820.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BBS9	ENST00000242067.11	c.1016+6873C>T		intron_variant	Intron 9 of 22	1	NM_198428.3	ENSP00000242067.6

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17006 AN: 149682 Hom.: 1127 Cov.: 31

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.0813

Gnomad AMR AF: 0.0735

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.0718

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.0836

Gnomad MID AF: 0.0960

Gnomad NFE AF: 0.0876

Gnomad OTH AF: 0.116

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

GnomAD4 genome AF: 0.114 AC: 17029 AN: 149778 Hom.: 1131 Cov.: 31 AF XY: 0.112 AC XY: 8199 AN XY: 72928

African (AFR) AF: 0.184 AC: 7460 AN: 40622

American (AMR) AF: 0.0734 AC: 1105 AN: 15046

Ashkenazi Jewish (ASJ) AF: 0.104 AC: 360 AN: 3470

East Asian (EAS) AF: 0.0720 AC: 366 AN: 5082

South Asian (SAS) AF: 0.136 AC: 645 AN: 4748

European-Finnish (FIN) AF: 0.0836 AC: 826 AN: 9884

Middle Eastern (MID) AF: 0.0935 AC: 26 AN: 278

European-Non Finnish (NFE) AF: 0.0876 AC: 5927 AN: 67656

Other (OTH) AF: 0.115 AC: 240 AN: 2082

Alfa AF: 0.102 Hom.: 132

Bravo AF: 0.118

Asia WGS AF: 0.0920 AC: 320 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.9
DANN	Benign	0.51
PhyloP100		-0.16
Mutation Taster		=99/1	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: rs10486525; hg19: chr7-33320441;