rs3815049

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003611.3(OFD1):c.1129+16A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 1,203,519 control chromosomes in the GnomAD database, including 34,154 homozygotes. There are 110,867 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 3488 hom., 9543 hem., cov: 22)

Exomes 𝑓: 0.28 ( 30666 hom. 101324 hem. )

Consequence

OFD1
NM_003611.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:13

Conservation

PhyloP100: -3.56

Publications

10 publications found

Variant links:

Genes affected

OFD1 (HGNC:2567): (OFD1 centriole and centriolar satellite protein) This gene is located on the X chromosome and encodes a centrosomal protein. A knockout mouse model has been used to study the effect of mutations in this gene. The mouse gene is also located on the X chromosome, however, unlike the human gene it is not subject to X inactivation. Mutations in this gene are associated with oral-facial-digital syndrome type I and Simpson-Golabi-Behmel syndrome type 2. Many pseudogenes have been identified; a single pseudogene is found on chromosome 5 while as many as fifteen have been found on the Y chromosome. [provided by RefSeq, Aug 2016]

OFD1 Gene-Disease associations (from GenCC):

Joubert syndrome 10
Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
OFD1-related ciliopathy
Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
orofaciodigital syndrome I
Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae)
retinitis pigmentosa 23
Inheritance: XL Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
primary ciliary dyskinesia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
retinitis pigmentosa
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
orofaciodigital syndrome type 6
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Simpson-Golabi-Behmel syndrome type 2
Inheritance: XL Classification: LIMITED Submitted by: G2P

OFD1 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 (BayesDel_noAF=-0.97).

BP6

Variant X-13753457-A-G is Benign according to our data. Variant chrX-13753457-A-G is described in ClinVar as Benign. ClinVar VariationId is 94370.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003611.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
OFD1	NM_003611.3	MANE Select	c.1129+16A>G	intron	N/A	NP_003602.1	O75665-1
OFD1	NM_001440947.1		c.1129+16A>G	intron	N/A	NP_001427876.1
OFD1	NM_001330209.2		c.1009+16A>G	intron	N/A	NP_001317138.1	O75665-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
OFD1	ENST00000340096.11	TSL:1 MANE Select	c.1129+16A>G	intron	N/A	ENSP00000344314.6	O75665-1
OFD1	ENST00000380550.6	TSL:1	c.1009+16A>G	intron	N/A	ENSP00000369923.3	O75665-3
OFD1	ENST00000922714.1		c.1132+16A>G	intron	N/A	ENSP00000592773.1

Frequencies

GnomAD3 genomes

AF:

0.288

AC:

31892

AN:

110845

Hom.:

3480

Cov.:

show subpopulations

Gnomad AFR

AF:

0.280

Gnomad AMI

AF:

0.194

Gnomad AMR

AF:

0.466

Gnomad ASJ

AF:

0.251

Gnomad EAS

AF:

0.442

Gnomad SAS

AF:

0.455

Gnomad FIN

AF:

0.234

Gnomad MID

AF:

0.283

Gnomad NFE

AF:

0.247

Gnomad OTH

AF:

0.300

GnomAD2 exomes

AF:

0.348

AC:

63613

AN:

182729

AF XY:

0.339

show subpopulations

Gnomad AFR exome

AF:

0.280

Gnomad AMR exome

AF:

0.650

Gnomad ASJ exome

AF:

0.243

Gnomad EAS exome

AF:

0.450

Gnomad FIN exome

AF:

0.254

Gnomad NFE exome

AF:

0.244

Gnomad OTH exome

AF:

0.314

GnomAD4 exome

AF:

0.277

AC:

302121

AN:

1092621

Hom.:

30666

Cov.:

AF XY:

0.282

AC XY:

101324

AN XY:

358671

show subpopulations

African (AFR)

AF:

0.277

AC:

7289

AN:

26304

American (AMR)

AF:

0.624

AC:

21946

AN:

35153

Ashkenazi Jewish (ASJ)

AF:

0.248

AC:

4787

AN:

19326

East Asian (EAS)

AF:

0.444

AC:

13391

AN:

30130

South Asian (SAS)

AF:

0.464

AC:

25028

AN:

53943

European-Finnish (FIN)

AF:

0.255

AC:

10317

AN:

40469

Middle Eastern (MID)

AF:

0.260

AC:

1058

AN:

4075

European-Non Finnish (NFE)

AF:

0.245

AC:

205321

AN:

837309

Other (OTH)

AF:

0.283

AC:

12984

AN:

45912

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

6613

13226

19840

26453

33066

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7714

15428

23142

30856

38570

<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:

0.288

AC:

31918

AN:

110898

Hom.:

3488

Cov.:

AF XY:

0.288

AC XY:

9543

AN XY:

33166

show subpopulations

African (AFR)

AF:

0.280

AC:

8544

AN:

30527

American (AMR)

AF:

0.467

AC:

4871

AN:

10435

Ashkenazi Jewish (ASJ)

AF:

0.251

AC:

661

AN:

2636

East Asian (EAS)

AF:

0.442

AC:

1553

AN:

3510

South Asian (SAS)

AF:

0.456

AC:

1198

AN:

2629

European-Finnish (FIN)

AF:

0.234

AC:

1379

AN:

5883

Middle Eastern (MID)

AF:

0.278

AC:

AN:

216

European-Non Finnish (NFE)

AF:

0.247

AC:

13060

AN:

52877

Other (OTH)

AF:

0.305

AC:

460

AN:

1506

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

813

1626

2438

3251

4064

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

328

656

984

1312

1640

<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:

0.266

Hom.:

2736

Bravo

AF:

0.312

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (6)

not provided (2)

Joubert syndrome 10 (1)

Orofaciodigital syndrome I (1)

Orofaciodigital syndrome I;C5979921:Joubert syndrome (1)

Retinitis pigmentosa 23 (1)

Simpson-Golabi-Behmel syndrome type 2 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.16

(source)

DANN

Benign

0.30

PhyloP100

-3.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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