NM_198428.3:c.1329+1016G>T

Variant names:

• chr7-33345650-G-T
• rs3884597
• NM_198428.3:c.1329+1016G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198428.3(BBS9):​c.1329+1016G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 151,954 control chromosomes in the GnomAD database, including 15,576 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 0.45 (15576 hom., cov: 32)
• Consequence: BBS9 NM_198428.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.177
• Publications: 8 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=-0.56).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198428.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BBS9	NM_198428.3	MANE Select	c.1329+1016G>T		intron	N/A	NP_940820.1
	BBS9	NM_001348041.4		c.1329+1016G>T		intron	N/A	NP_001334970.1
	BBS9	NM_001348036.1		c.1329+1016G>T		intron	N/A	NP_001334965.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BBS9	ENST00000242067.11	TSL:1 MANE Select	c.1329+1016G>T		intron	N/A	ENSP00000242067.6
	BBS9	ENST00000434373.3	TSL:1	c.27+1016G>T		intron	N/A	ENSP00000388114.1
	BBS9	ENST00000433714.5	TSL:1	n.1330-577G>T		intron	N/A	ENSP00000412159.1

Frequencies

GnomAD3 genomes AF: 0.449 AC: 68187 AN: 151836 Hom.: 15572 Cov.: 32

Gnomad AFR AF: 0.374

Gnomad AMI AF: 0.455

Gnomad AMR AF: 0.531

Gnomad ASJ AF: 0.523

Gnomad EAS AF: 0.458

Gnomad SAS AF: 0.465

Gnomad FIN AF: 0.473

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.466

Gnomad OTH AF: 0.474

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

GnomAD4 genome AF: 0.449 AC: 68228 AN: 151954 Hom.: 15576 Cov.: 32 AF XY: 0.453 AC XY: 33649 AN XY: 74252

African (AFR) AF: 0.374 AC: 15476 AN: 41434

American (AMR) AF: 0.532 AC: 8117 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.523 AC: 1813 AN: 3466

East Asian (EAS) AF: 0.459 AC: 2372 AN: 5170

South Asian (SAS) AF: 0.464 AC: 2231 AN: 4808

European-Finnish (FIN) AF: 0.473 AC: 4981 AN: 10530

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.466 AC: 31686 AN: 67962

Other (OTH) AF: 0.473 AC: 997 AN: 2108

Alfa AF: 0.463 Hom.: 46370

Bravo AF: 0.452

Asia WGS AF: 0.463 AC: 1611 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	8.3
DANN	Benign	0.55
PhyloP100		0.18
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: rs3884597; hg19: chr7-33385262;