rs3750123

Variant names:

• chr7-33129646-C-G
• rs3750123
• NM_198428.3:c.-407C>G

Your query was ambiguous. Multiple possible variants found:

• chr7-33129646-C-G
• chr7-33129646-C-T

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.-407C>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 152,934 control chromosomes in the GnomAD database, including 2,157 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.16 (2141 hom., cov: 32)
  • Exomes 𝑓: 0.19 (16 hom.)
• Consequence: BBS9 NM_198428.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0600
• Publications: 4 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 7-33129646-C-G is Benign according to our data. Variant chr7-33129646-C-G is described in ClinVar as Benign. ClinVar VariationId is 360051.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.-407C>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 23	NP_940820.1	Q3SYG4-1
	BBS9	NM_198428.3	MANE Select	c.-407C>G		5_prime_UTR	Exon 1 of 23	NP_940820.1	Q3SYG4-1
	BBS9	NM_001348041.4		c.-407C>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 23	NP_001334970.1	A0A5F9ZH14

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BBS9	ENST00000242067.11	TSL:1 MANE Select	c.-407C>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 23	ENSP00000242067.6	Q3SYG4-1
	BBS9	ENST00000242067.11	TSL:1 MANE Select	c.-407C>G		5_prime_UTR	Exon 1 of 23	ENSP00000242067.6	Q3SYG4-1
	BBS9	ENST00000433714.5	TSL:1	n.-407C>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 24	ENSP00000412159.1	F8WCG5

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24622 AN: 151976 Hom.: 2136 Cov.: 32

Gnomad AFR AF: 0.0975

Gnomad AMI AF: 0.0846

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.208

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.179

GnomAD4 exome AF: 0.190 AC: 160 AN: 840 Hom.: 16 Cov.: 0 AF XY: 0.195 AC XY: 108 AN XY: 554

African (AFR) AF: 0.188 AC: 6 AN: 32

American (AMR) AF: 0.167 AC: 1 AN: 6

Ashkenazi Jewish (ASJ) AF: 0.300 AC: 3 AN: 10

East Asian (EAS) AF: 0.192 AC: 5 AN: 26

South Asian (SAS) AF: 0.286 AC: 20 AN: 70

European-Finnish (FIN) AF: 0.192 AC: 5 AN: 26

Middle Eastern (MID) AF: 0.250 AC: 2 AN: 8

European-Non Finnish (NFE) AF: 0.180 AC: 111 AN: 616

Other (OTH) AF: 0.152 AC: 7 AN: 46

GnomAD4 genome AF: 0.162 AC: 24657 AN: 152094 Hom.: 2141 Cov.: 32 AF XY: 0.164 AC XY: 12173 AN XY: 74350

African (AFR) AF: 0.0981 AC: 4072 AN: 41520

American (AMR) AF: 0.179 AC: 2735 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 631 AN: 3470

East Asian (EAS) AF: 0.154 AC: 792 AN: 5150

South Asian (SAS) AF: 0.215 AC: 1035 AN: 4814

European-Finnish (FIN) AF: 0.208 AC: 2201 AN: 10574

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.186 AC: 12675 AN: 67982

Other (OTH) AF: 0.181 AC: 382 AN: 2110

Alfa AF: 0.176 Hom.: 307

Bravo AF: 0.156

Asia WGS AF: 0.201 AC: 698 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	6.9
DANN	Benign	0.62
PhyloP100		-0.060
PromoterAI		0.10	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=300/0	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: rs3750123; hg19: chr7-33169258;