rs140821420

Variant names:

• chr7-33273045-C-G
• NM_198428.3:c.736C>G

Your query was ambiguous. Multiple possible variants found:

• chr7-33273045-C-G
• chr7-33273045-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_198428.3(BBS9):​c.736C>G​(p.Leu246Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,528 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: BBS9 NM_198428.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.14

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26669282).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BBS9	NM_198428.3	c.736C>G	p.Leu246Val	missense_variant	Exon 8 of 23	ENST00000242067.11	NP_940820.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BBS9	ENST00000242067.11	c.736C>G	p.Leu246Val	missense_variant	Exon 8 of 23	1	NM_198428.3	ENSP00000242067.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461528 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727066

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

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	0.077
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.086	T;.;.;.;.;T
Eigen	Benign	-0.11
Eigen_PC	Benign	0.070
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.87	D;T;D;D;T;T
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.27	T;T;T;T;T;T
MetaSVM	Benign	-0.54	T
MutationAssessor	Benign	1.9	L;L;L;L;.;.
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.4	N;N;N;N;N;N
REVEL	Uncertain	0.43
Sift	Benign	0.20	T;T;T;T;T;T
Sift4G	Benign	0.17	T;T;T;T;T;T
Polyphen		0.044	B;B;B;.;.;.
Vest4		0.62
MutPred		0.23		Loss of catalytic residue at L246 (P = 0.031);Loss of catalytic residue at L246 (P = 0.031);Loss of catalytic residue at L246 (P = 0.031);Loss of catalytic residue at L246 (P = 0.031);.;.;
MVP		0.69
MPC		0.066
ClinPred		0.69	D
GERP RS		4.9
Varity_R		0.35
gMVP		0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr7-33312657;