chr7-33341061-T-C

Position:

• chr7-33341061-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.1275+88T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 1,146,312 control chromosomes in the GnomAD database, including 41,763 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.26 (5534 hom., cov: 31)
  • Exomes 𝑓: 0.26 (36229 hom.)
• Consequence: BBS9 NM_198428.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.309

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 7-33341061-T-C is Benign according to our data. Variant chr7-33341061-T-C is described in ClinVar as [Benign]. Clinvar id is 1237819.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BBS9	NM_198428.3	c.1275+88T>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.1275+88T>C		intron_variant		1	NM_198428.3	ENSP00000242067	P3

Frequencies

GnomAD3 genomes AF: 0.264 AC: 40104 AN: 151776 Hom.: 5533 Cov.: 31

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.442

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.0742

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.304

Gnomad OTH AF: 0.250

GnomAD4 exome AF: 0.263 AC: 261284 AN: 994418 Hom.: 36229 AF XY: 0.262 AC XY: 134681 AN XY: 514118

Gnomad4 AFR exome AF: 0.239

Gnomad4 AMR exome AF: 0.147

Gnomad4 ASJ exome AF: 0.245

Gnomad4 EAS exome AF: 0.0489

Gnomad4 SAS exome AF: 0.211

Gnomad4 FIN exome AF: 0.269

Gnomad4 NFE exome AF: 0.288

Gnomad4 OTH exome AF: 0.262

GnomAD4 genome AF: 0.264 AC: 40112 AN: 151894 Hom.: 5534 Cov.: 31 AF XY: 0.258 AC XY: 19182 AN XY: 74244

Gnomad4 AFR AF: 0.246

Gnomad4 AMR AF: 0.208

Gnomad4 ASJ AF: 0.247

Gnomad4 EAS AF: 0.0742

Gnomad4 SAS AF: 0.217

Gnomad4 FIN AF: 0.267

Gnomad4 NFE AF: 0.304

Gnomad4 OTH AF: 0.247

Alfa AF: 0.172 Hom.: 346

Bravo AF: 0.258

Asia WGS AF: 0.141 AC: 493 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	-0.88
CADD	Benign	3.7
DANN	Benign	0.57

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: rs10486527; hg19: chr7-33380673; COSMIC: COSV54169406; COSMIC: COSV54169406;