rs6944723

Positions:

• chr7-33384348-T-A
• chr7-33384348-T-C

Variant summary

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

The NM_198428.3(BBS9):​c.1962+510T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 152,068 control chromosomes in the GnomAD database, including 13,499 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 0.42 (13499 hom., cov: 32)
• Consequence: BBS9 NM_198428.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.701

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BBS9	NM_198428.3	c.1962+510T>A		intron_variant		ENST00000242067.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BBS9	ENST00000242067.11	c.1962+510T>A		intron_variant		1	NM_198428.3	P3

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63565 AN: 151950 Hom.: 13487 Cov.: 32

Gnomad AFR AF: 0.407

Gnomad AMI AF: 0.446

Gnomad AMR AF: 0.380

Gnomad ASJ AF: 0.342

Gnomad EAS AF: 0.467

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.452

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.432

Gnomad OTH AF: 0.389

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

GnomAD4 genome AF: 0.418 AC: 63632 AN: 152068 Hom.: 13499 Cov.: 32 AF XY: 0.417 AC XY: 31010 AN XY: 74356

Gnomad4 AFR AF: 0.407

Gnomad4 AMR AF: 0.380

Gnomad4 ASJ AF: 0.342

Gnomad4 EAS AF: 0.467

Gnomad4 SAS AF: 0.386

Gnomad4 FIN AF: 0.452

Gnomad4 NFE AF: 0.432

Gnomad4 OTH AF: 0.392

Alfa AF: 0.435 Hom.: 1840

Bravo AF: 0.409

Asia WGS AF: 0.434 AC: 1510 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.9
DANN	Benign	0.25

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: rs6944723; hg19: chr7-33423960;