chr7-33510429-C-T

Position:

• chr7-33510429-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000242067.11(BBS9):​c.2298+4784C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0905 in 151,984 control chromosomes in the GnomAD database, including 689 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 0.090 (689 hom., cov: 32)
• Consequence: BBS9 ENST00000242067.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0850

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.133 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BBS9	NM_198428.3	c.2298+4784C>T		intron_variant		ENST00000242067.11	NP_940820.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BBS9	ENST00000242067.11	c.2298+4784C>T		intron_variant		1	NM_198428.3	ENSP00000242067	P3

Frequencies

GnomAD3 genomes AF: 0.0905 AC: 13743 AN: 151864 Hom.: 688 Cov.: 32

Gnomad AFR AF: 0.0760

Gnomad AMI AF: 0.0855

Gnomad AMR AF: 0.0723

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.0568

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.0359

Gnomad MID AF: 0.0924

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.105

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

GnomAD4 genome AF: 0.0905 AC: 13749 AN: 151984 Hom.: 689 Cov.: 32 AF XY: 0.0874 AC XY: 6496 AN XY: 74296

Gnomad4 AFR AF: 0.0760

Gnomad4 AMR AF: 0.0722

Gnomad4 ASJ AF: 0.108

Gnomad4 EAS AF: 0.0568

Gnomad4 SAS AF: 0.142

Gnomad4 FIN AF: 0.0359

Gnomad4 NFE AF: 0.110

Gnomad4 OTH AF: 0.103

Alfa AF: 0.106 Hom.: 1252

Bravo AF: 0.0935

Asia WGS AF: 0.0840 AC: 294 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.4
DANN	Benign	0.70

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: rs10262995; hg19: chr7-33550041;