rs1468797

Variant names:

• chr7-33130048-T-C
• rs1468797
• NM_198428.3:c.-12+7T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_198428.3(BBS9):​c.-12+7T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 152,182 control chromosomes in the GnomAD database, including 2,033 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.15 (2033 hom., cov: 32)
  • Exomes 𝑓: 0.22 (0 hom.)
• Consequence: BBS9 NM_198428.3 splice_region, intron
• Scores: Splicing: ADA: 0.00003683
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0120
• 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: Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp
• BBS9-related 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 7-33130048-T-C is Benign according to our data. Variant chr7-33130048-T-C is described in ClinVar as Benign. ClinVar VariationId is 360059.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.204 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BBS9	NM_198428.3	MANE Select	c.-12+7T>C		splice_region intron	N/A	NP_940820.1	Q3SYG4-1
	BBS9	NM_001348041.4		c.-12+7T>C		splice_region intron	N/A	NP_001334970.1	A0A5F9ZH14
	BBS9	NM_001348036.1		c.-12+496T>C		intron	N/A	NP_001334965.1	Q3SYG4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BBS9	ENST00000242067.11	TSL:1 MANE Select	c.-12+7T>C		splice_region intron	N/A	ENSP00000242067.6	Q3SYG4-1
	BBS9	ENST00000433714.5	TSL:1	n.-12+7T>C		splice_region intron	N/A	ENSP00000412159.1	F8WCG5
	BBS9	ENST00000942912.1		c.-12+7T>C		splice_region intron	N/A	ENSP00000612971.1

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23532 AN: 152032 Hom.: 2033 Cov.: 32

Gnomad AFR AF: 0.0760

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.208

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.167

GnomAD4 exome AF: 0.219 AC: 7 AN: 32 Hom.: 0 Cov.: 0 AF XY: 0.222 AC XY: 4 AN XY: 18

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.500 AC: 1 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.417 AC: 5 AN: 12

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.100 AC: 1 AN: 10

Other (OTH) AF: 0.00 AC: 0 AN: 8

GnomAD4 genome AF: 0.155 AC: 23560 AN: 152150 Hom.: 2033 Cov.: 32 AF XY: 0.156 AC XY: 11636 AN XY: 74362

African (AFR) AF: 0.0765 AC: 3175 AN: 41520

American (AMR) AF: 0.172 AC: 2622 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 630 AN: 3470

East Asian (EAS) AF: 0.153 AC: 793 AN: 5176

South Asian (SAS) AF: 0.215 AC: 1035 AN: 4822

European-Finnish (FIN) AF: 0.208 AC: 2193 AN: 10568

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.186 AC: 12623 AN: 67994

Other (OTH) AF: 0.169 AC: 357 AN: 2110

Alfa AF: 0.170 Hom.: 687

Bravo AF: 0.148

Asia WGS AF: 0.200 AC: 694 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Bardet-Biedl syndrome 9 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	8.2
DANN	Benign	0.80
PhyloP100		-0.012
PromoterAI		0.020	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000037
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.14		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: rs1468797; hg19: chr7-33169660;