rs4924987

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 10/11 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

Publications

28 publications found

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 Gene-Disease associations (from GenCC):

ciliopathy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
Joubert syndrome 27
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
Meckel syndrome, type 9
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Genomics England PanelApp, G2P
Joubert syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Meckel syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

B9D1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 260675.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001321215.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
B9D1	NM_015681.6	MANE Select	c.472+28C>T		intron	N/A	NP_056496.1
B9D1	NM_001321215.3		c.500C>T	p.Pro167Leu	missense	Exon 6 of 6	NP_001308144.1
B9D1	NM_001321214.2		c.472+28C>T		intron	N/A	NP_001308143.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
B9D1	ENST00000261499.11	TSL:1 MANE Select	c.472+28C>T		intron	N/A	ENSP00000261499.4
B9D1	ENST00000663089.1		c.563C>T	p.Pro188Leu	missense	Exon 7 of 7	ENSP00000499469.1
B9D1	ENST00000647252.1		c.500C>T	p.Pro167Leu	missense	Exon 6 of 6	ENSP00000495045.1

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

GnomAD2 exomes

AF:

0.600

AC:

150429

AN:

250814

AF XY:

0.612

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 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

African (AFR)

AF:

0.154

AC:

5169

AN:

33476

American (AMR)

AF:

0.440

AC:

19666

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.836

AC:

21847

AN:

26136

East Asian (EAS)

AF:

0.00322

AC:

128

AN:

39698

South Asian (SAS)

AF:

0.392

AC:

33781

AN:

86250

European-Finnish (FIN)

AF:

0.792

AC:

42257

AN:

53378

Middle Eastern (MID)

AF:

0.658

AC:

3794

AN:

5768

European-Non Finnish (NFE)

AF:

0.813

AC:

904486

AN:

1111948

Other (OTH)

AF:

0.684

AC:

41298

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

14906

29812

44719

59625

74531

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20196

40392

60588

80784

100980

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.564

AC:

85810

AN:

152132

Hom.:

30917

Cov.:

AF XY:

0.553

AC XY:

41140

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.178

AC:

7393

AN:

41510

American (AMR)

AF:

0.540

AC:

8253

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.843

AC:

2928

AN:

3472

East Asian (EAS)

AF:

0.00657

AC:

AN:

5172

South Asian (SAS)

AF:

0.343

AC:

1653

AN:

4822

European-Finnish (FIN)

AF:

0.778

AC:

8236

AN:

10582

Middle Eastern (MID)

AF:

0.660

AC:

194

AN:

294

European-Non Finnish (NFE)

AF:

0.809

AC:

54962

AN:

67966

Other (OTH)

AF:

0.616

AC:

1300

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1265

2531

3796

5062

6327

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

658

1316

1974

2632

3290

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.717

Hom.:

12206

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

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (3)

Meckel syndrome, type 9 (2)

Joubert syndrome 27 (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.65

CADD

Benign

0.48

(source)

DANN

Benign

0.39

FATHMM_MKL

Benign

0.082

MetaRNN

Benign

9.2e-7

PhyloP100

-0.25

PrimateAI

Benign

0.27

Sift4G

Benign

0.32

Vest4

0.045

GERP RS

-0.60

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over