7-33146286-A-G

Position:

chr7-33146286-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_198428.3(BBS9):c.34A>G(p.Thr12Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00246 in 1,614,020 control chromosomes in the GnomAD database, including 85 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 49 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 36 hom. )

Consequence

BBS9
NM_198428.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.46

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0032102764).

BP6

Variant 7-33146286-A-G is Benign according to our data. Variant chr7-33146286-A-G is described in ClinVar as [Benign]. Clinvar id is 263130.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-33146286-A-G is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0128 (1954/152310) while in subpopulation AFR AF= 0.0448 (1861/41550). AF 95% confidence interval is 0.0431. There are 49 homozygotes in gnomad4. There are 923 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 49 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BBS9	NM_198428.3 linkuse as main transcript	c.34A>G	p.Thr12Ala	missense_variant	2/23	ENST00000242067.11	NP_940820.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BBS9	ENST00000242067.11 linkuse as main transcript	c.34A>G	p.Thr12Ala	missense_variant	2/23	1	NM_198428.3	ENSP00000242067	P3	Q3SYG4-1

Frequencies

GnomAD3 genomes

AF:

0.0127

AC:

1939

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0446

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00406

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00764

GnomAD3 exomes

AF:

0.00334

AC:

839

AN:

251472

Hom.:

AF XY:

0.00255

AC XY:

346

AN XY:

135912

show subpopulations

Gnomad AFR exome

AF:

0.0447

Gnomad AMR exome

AF:

0.00208

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00101

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.00138

AC:

2017

AN:

1461710

Hom.:

Cov.:

AF XY:

0.00122

AC XY:

885

AN XY:

727178

show subpopulations

Gnomad4 AFR exome

AF:

0.0480

Gnomad4 AMR exome

AF:

0.00219

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000939

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000234

Gnomad4 OTH exome

AF:

0.00321

GnomAD4 genome

AF:

0.0128

AC:

1954

AN:

152310

Hom.:

Cov.:

AF XY:

0.0124

AC XY:

923

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.0448

Gnomad4 AMR

AF:

0.00405

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00756

Alfa

AF:

0.00209

Hom.:

Bravo

AF:

0.0144

ESP6500AA

AF:

0.0402

AC:

177

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00413

AC:

501

Asia WGS

AF:

0.00491

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Bardet-Biedl syndrome 9

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Bardet-Biedl syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.055

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.12

T;T;.;.;.

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.21

FATHMM_MKL

Benign

0.69

LIST_S2

Uncertain

0.88

D;D;D;D;D

MetaRNN

Benign

0.0032

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.52

.;N;N;N;N

MutationTaster

Benign

1.0

D;N;N;N;N;N

PrimateAI

Benign

0.47

PROVEAN

Benign

-2.3

N;D;N;D;D

REVEL

Benign

0.23

Sift

Benign

0.28

T;T;T;T;T

Sift4G

Benign

0.42

T;T;T;T;T

Polyphen

0.014

.;B;B;B;.

Vest4

0.11, 0.15, 0.10

MVP

0.72

MPC

0.080

ClinPred

0.013

GERP RS

2.8

Varity_R

0.27

gMVP

0.41

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over