Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_003611.3(OFD1):c.1654+9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000622 in 1,011,601 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 173 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00041 ( 0 hom., 10 hem., cov: 22)

Exomes 𝑓: 0.00065 ( 0 hom. 163 hem. )

Consequence

OFD1
NM_003611.3 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.0740

Publications

0 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):

ciliopathy
Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
Joubert syndrome 10
Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
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: G2P, Labcorp Genetics (formerly Invitae)
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=-0.67).

BP6

Variant X-13758457-C-T is Benign according to our data. Variant chrX-13758457-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 463450.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAdExome4 allele frequency = 0.000648 (583/900060) while in subpopulation NFE AF = 0.000785 (521/663691). AF 95% confidence interval is 0.000729. There are 0 homozygotes in GnomAdExome4. There are 163 alleles in the male GnomAdExome4 subpopulation. Median coverage is 17. This position passed quality control check.

BS2

High Hemizygotes in GnomAd4 at 10 XL,AD,AR gene

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
OFD1	NM_003611.3	MANE Select	c.1654+9C>T	intron	N/A	NP_003602.1
OFD1	NM_001440947.1		c.1654+9C>T	intron	N/A	NP_001427876.1
OFD1	NM_001330209.2		c.1534+9C>T	intron	N/A	NP_001317138.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
OFD1	ENST00000340096.11	TSL:1 MANE Select	c.1654+9C>T	intron	N/A	ENSP00000344314.6
OFD1	ENST00000380550.6	TSL:1	c.1534+9C>T	intron	N/A	ENSP00000369923.3
OFD1	ENST00000464463.6	TSL:3	n.1826C>T	non_coding_transcript_exon	Exon 14 of 21

Frequencies

GnomAD3 genomes

AF:

0.000413

AC:

AN:

111490

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000979

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000573

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000682

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000602

Gnomad OTH

AF:

0.000668

GnomAD2 exomes

AF:

0.000505

AC:

AN:

178281

AF XY:

0.000394

show subpopulations

Gnomad AFR exome

AF:

0.000158

Gnomad AMR exome

AF:

0.0000746

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000147

Gnomad FIN exome

AF:

0.000565

Gnomad NFE exome

AF:

0.000891

Gnomad OTH exome

AF:

0.000681

GnomAD4 exome

AF:

0.000648

AC:

583

AN:

900060

Hom.:

Cov.:

AF XY:

0.000682

AC XY:

163

AN XY:

238954

show subpopulations

African (AFR)

AF:

0.0000887

AC:

AN:

22549

American (AMR)

AF:

0.000116

AC:

AN:

34559

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18107

East Asian (EAS)

AF:

0.000136

AC:

AN:

29325

South Asian (SAS)

AF:

0.0000406

AC:

AN:

49208

European-Finnish (FIN)

AF:

0.000694

AC:

AN:

40333

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2700

European-Non Finnish (NFE)

AF:

0.000785

AC:

521

AN:

663691

Other (OTH)

AF:

0.000556

AC:

AN:

39588

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.000412

AC:

AN:

111541

Hom.:

Cov.:

AF XY:

0.000296

AC XY:

AN XY:

33749

show subpopulations

African (AFR)

AF:

0.0000977

AC:

AN:

30721

American (AMR)

AF:

0.000572

AC:

AN:

10484

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2643

East Asian (EAS)

AF:

0.00

AC:

AN:

3568

South Asian (SAS)

AF:

0.00

AC:

AN:

2695

European-Finnish (FIN)

AF:

0.000682

AC:

AN:

5866

Middle Eastern (MID)

AF:

0.00

AC:

AN:

217

European-Non Finnish (NFE)

AF:

0.000602

AC:

AN:

53144

Other (OTH)

AF:

0.000659

AC:

AN:

1517

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.000477

Hom.:

Bravo

AF:

0.000506

ClinVar

ClinVar submissions as Germline

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Joubert syndrome;C1510460:Orofaciodigital syndrome I (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

2.2

(source)

DANN

Benign

0.76

PhyloP100

0.074

Mutation Taster

=100/0

polymorphism

(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.

rs200007045

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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over