rs4924987

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001321215.3(B9D1):c.500C>T(p.Pro167Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.718 in 1,613,886 control chromosomes in the GnomAD database, including 453,330 homozygotes. In-silico tool predicts a benign outcome for this variant. 9/10 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.56 ( 30917 hom., cov: 33)

Exomes 𝑓: 0.73 ( 422413 hom. )

Consequence

B9D1
NM_001321215.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.254

Variant links:

Genes affected

B9D1 (HGNC:24123): (B9 domain containing 1) This gene encodes a B9 domain-containing protein, one of several that are involved in ciliogenesis. Alterations in expression of this gene have been found in a family with Meckel syndrome. Meckel syndrome has been associated with at least six different genes. This gene is located within the Smith-Magenis syndrome region on chromosome 17. [provided by RefSeq, Mar 2016]

B9D1 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=9.1532996E-7).

BP6

Variant 17-19343762-G-A is Benign according to our data. Variant chr17-19343762-G-A is described in ClinVar as [Benign]. Clinvar id is 260675.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-19343762-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.803 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
B9D1	NM_015681.6 link	c.472+28C>T		intron_variant	Intron 6 of 6	ENST00000261499.11	NP_056496.1	Q9UPM9-1B4DEW0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
B9D1	ENST00000261499.11 link	c.472+28C>T		intron_variant	Intron 6 of 6	1	NM_015681.6	ENSP00000261499.4		Q9UPM9-1

Frequencies

GnomAD3 genomes

AF:

0.565

AC:

85823

AN:

152014

Hom.:

30924

Cov.:

show subpopulations

Gnomad AFR

AF:

0.179

Gnomad AMI

AF:

0.940

Gnomad AMR

AF:

0.540

Gnomad ASJ

AF:

0.843

Gnomad EAS

AF:

0.00637

Gnomad SAS

AF:

0.341

Gnomad FIN

AF:

0.778

Gnomad MID

AF:

0.655

Gnomad NFE

AF:

0.809

Gnomad OTH

AF:

0.623

GnomAD3 exomes

AF:

0.600

AC:

150429

AN:

250814

Hom.:

54941

AF XY:

0.612

AC XY:

82967

AN XY:

135636

show subpopulations

Gnomad AFR exome

AF:

0.165

Gnomad AMR exome

AF:

0.425

Gnomad ASJ exome

AF:

0.835

Gnomad EAS exome

AF:

0.00251

Gnomad SAS exome

AF:

0.378

Gnomad FIN exome

AF:

0.786

Gnomad NFE exome

AF:

0.810

Gnomad OTH exome

AF:

0.691

GnomAD4 exome

AF:

0.734

AC:

1072426

AN:

1461754

Hom.:

422413

Cov.:

AF XY:

0.728

AC XY:

529033

AN XY:

727176

show subpopulations

Gnomad4 AFR exome

AF:

0.154

Gnomad4 AMR exome

AF:

0.440

Gnomad4 ASJ exome

AF:

0.836

Gnomad4 EAS exome

AF:

0.00322

Gnomad4 SAS exome

AF:

0.392

Gnomad4 FIN exome

AF:

0.792

Gnomad4 NFE exome

AF:

0.813

Gnomad4 OTH exome

AF:

0.684

GnomAD4 genome

AF:

0.564

AC:

85810

AN:

152132

Hom.:

30917

Cov.:

AF XY:

0.553

AC XY:

41140

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.178

Gnomad4 AMR

AF:

0.540

Gnomad4 ASJ

AF:

0.843

Gnomad4 EAS

AF:

0.00657

Gnomad4 SAS

AF:

0.343

Gnomad4 FIN

AF:

0.778

Gnomad4 NFE

AF:

0.809

Gnomad4 OTH

AF:

0.616

Alfa

AF:

0.726

Hom.:

12185

Bravo

AF:

0.533

TwinsUK

AF:

0.812

AC:

3010

ALSPAC

AF:

0.802

AC:

3090

ESP6500AA

AF:

0.195

AC:

860

ESP6500EA

AF:

0.807

AC:

6938

ExAC

AF:

0.597

AC:

72454

Asia WGS

AF:

0.170

AC:

593

AN:

3478

EpiCase

AF:

0.807

EpiControl

AF:

0.799

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Jan 08, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Meckel syndrome, type 9

Benign:2

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Joubert syndrome 27

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.65

CADD

Benign

0.48

DANN

Benign

0.39

FATHMM_MKL

Benign

0.082

MetaRNN

Benign

9.2e-7

T;T

PrimateAI

Benign

0.27

Sift4G

Benign

0.32

T;.

Vest4

0.045

GERP RS

-0.60

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

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