7-33145997-T-C

Position:

• chr7-33145997-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_198428.3(BBS9):​c.-11-245T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 152,276 control chromosomes in the GnomAD database, including 2,076 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.16 (2076 hom., cov: 32)
• Consequence: BBS9 NM_198428.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.827

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 7-33145997-T-C is Benign according to our data. Variant chr7-33145997-T-C is described in ClinVar as [Benign]. Clinvar id is 1283381.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BBS9	NM_198428.3	c.-11-245T>C		intron_variant		ENST00000242067.11	NP_940820.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BBS9	ENST00000242067.11	c.-11-245T>C		intron_variant		1	NM_198428.3	ENSP00000242067.6

Frequencies

GnomAD3 genomes AF: 0.158 AC: 24009 AN: 152158 Hom.: 2072 Cov.: 32

Gnomad AFR AF: 0.0837

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.208

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.175

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

GnomAD4 genome AF: 0.158 AC: 24043 AN: 152276 Hom.: 2076 Cov.: 32 AF XY: 0.160 AC XY: 11898 AN XY: 74444

Gnomad4 AFR AF: 0.0843

Gnomad4 AMR AF: 0.177

Gnomad4 ASJ AF: 0.182

Gnomad4 EAS AF: 0.154

Gnomad4 SAS AF: 0.214

Gnomad4 FIN AF: 0.208

Gnomad4 NFE AF: 0.186

Gnomad4 OTH AF: 0.178

Alfa AF: 0.173 Hom.: 395

Bravo AF: 0.151

Asia WGS AF: 0.201 AC: 697 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.0
DANN	Benign	0.40

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

Publications

LitVar

Other links and lift over

dbSNP: rs13244450; hg19: chr7-33185609;