rs6944723

Variant names:

• chr7-33384348-T-A
• rs6944723
• NM_198428.3:c.1962+510T>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• 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=-0.9).
• 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 rank	MANE	Protein	UniProt
BBS9	NM_198428.3	c.1962+510T>A		intron_variant	Intron 18 of 22	ENST00000242067.11	NP_940820.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BBS9	ENST00000242067.11	c.1962+510T>A		intron_variant	Intron 18 of 22	1	NM_198428.3	ENSP00000242067.6

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

African (AFR) AF: 0.407 AC: 16879 AN: 41458

American (AMR) AF: 0.380 AC: 5808 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.342 AC: 1187 AN: 3472

East Asian (EAS) AF: 0.467 AC: 2413 AN: 5170

South Asian (SAS) AF: 0.386 AC: 1864 AN: 4828

European-Finnish (FIN) AF: 0.452 AC: 4775 AN: 10570

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.432 AC: 29367 AN: 67970

Other (OTH) AF: 0.392 AC: 826 AN: 2108

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
PhyloP100		0.70
Mutation Taster		=100/0	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: rs6944723; hg19: chr7-33423960;