7-33383725-A-G

Variant names:

• chr7-33383725-A-G
• NM_198428.3:c.1849A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_198428.3(BBS9):​c.1849A>G​(p.Ile617Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,906 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I617L) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: BBS9 NM_198428.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.75

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1781806).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BBS9	NM_198428.3	c.1849A>G	p.Ile617Val	missense_variant	Exon 18 of 23	ENST00000242067.11	NP_940820.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BBS9	ENST00000242067.11	c.1849A>G	p.Ile617Val	missense_variant	Exon 18 of 23	1	NM_198428.3	ENSP00000242067.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459906 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726110

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000188

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	16
DANN	Benign	0.86
DEOGEN2	Benign	0.018	T;.;.;.
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.88	D;D;D;D
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.18	T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.76	N;.;.;.
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.15	N;N;N;N
REVEL	Benign	0.056
Sift	Benign	0.60	T;T;T;T
Sift4G	Benign	0.66	T;T;T;T
Polyphen		0.015	B;B;B;.
Vest4		0.18
MutPred		0.26		Loss of catalytic residue at L618 (P = 0.4062);.;.;.;
MVP		0.31
MPC		0.059
ClinPred		0.71	D
GERP RS		6.1
Varity_R		0.091
gMVP		0.082

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-33423337;