rs863224534

Variant names:

• chr7-33349161-G-C
• rs863224534
• NM_198428.3:c.1423G>C

Your query was ambiguous. Multiple possible variants found:

• chr7-33349161-G-C
• chr7-33349161-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001348041.4(BBS9):​c.1423G>C​(p.Glu475Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. E475E) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BBS9 NM_001348041.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.34
• Publications: 1 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16463727).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001348041.4. 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.1423G>C	p.Glu475Gln	missense	Exon 13 of 23	NP_940820.1
	BBS9	NM_001348041.4		c.1423G>C	p.Glu475Gln	missense	Exon 13 of 23	NP_001334970.1
	BBS9	NM_001348036.1		c.1423G>C	p.Glu475Gln	missense	Exon 13 of 23	NP_001334965.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BBS9	ENST00000242067.11	TSL:1 MANE Select	c.1423G>C	p.Glu475Gln	missense	Exon 13 of 23	ENSP00000242067.6
	BBS9	ENST00000434373.3	TSL:1	c.121G>C	p.Glu41Gln	missense	Exon 2 of 11	ENSP00000388114.1
	BBS9	ENST00000433714.5	TSL:1	n.*184G>C		non_coding_transcript_exon	Exon 14 of 24	ENSP00000412159.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.028	T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.059
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PhyloP100		1.3
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.50	N
REVEL	Benign	0.073
Sift	Benign	0.36	T
Sift4G	Benign	0.50	T
Polyphen		0.27	B
Vest4		0.11
MutPred		0.31		Loss of sheet (P = 0.0817)
MVP		0.69
MPC		0.16
ClinPred		0.32	T
GERP RS		4.5
Varity_R		0.20
gMVP		0.29
Mutation Taster		=87/13	polymorphism

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: rs863224534; hg19: chr7-33388773; COSMIC: COSV54185225; COSMIC: COSV54185225;