Variant rs201761130 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_003611.3(OFD1):c.1543-19C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000567 in 1,049,732 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 180 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.00041 ( 0 hom., 13 hem., cov: 22)

Exomes 𝑓: 0.00059 ( 0 hom. 167 hem. )

Consequence

OFD1
NM_003611.3 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.687

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

This place is a probable branch point but likely benign (scored 1 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant X-13758318-C-G is Benign according to our data. Variant chrX-13758318-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 259095.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Hemizygotes in GnomAd4 at 13 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OFD1	NM_003611.3 linkuse as main transcript	c.1543-19C>G		intron_variant		ENST00000340096.11	NP_003602.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OFD1	ENST00000340096.11 linkuse as main transcript	c.1543-19C>G		intron_variant		1	NM_003611.3	ENSP00000344314	P1	O75665-1

Frequencies

GnomAD3 genomes

AF:

0.000413

AC:

AN:

111256

Hom.:

Cov.:

AF XY:

0.000389

AC XY:

AN XY:

33448

show subpopulations

Gnomad AFR

AF:

0.0000653

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000480

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000715

Gnomad OTH

AF:

0.000672

GnomAD3 exomes

AF:

0.000312

AC:

AN:

179539

Hom.:

AF XY:

0.000326

AC XY:

AN XY:

64437

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000371

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000547

Gnomad OTH exome

AF:

0.000451

GnomAD4 exome

AF:

0.000585

AC:

549

AN:

938421

Hom.:

Cov.:

AF XY:

0.000628

AC XY:

167

AN XY:

265769

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000374

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000248

Gnomad4 NFE exome

AF:

0.000741

Gnomad4 OTH exome

AF:

0.000442

GnomAD4 genome

AF:

0.000413

AC:

AN:

111311

Hom.:

Cov.:

AF XY:

0.000388

AC XY:

AN XY:

33513

show subpopulations

Gnomad4 AFR

AF:

0.0000652

Gnomad4 AMR

AF:

0.000479

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000715

Gnomad4 OTH

AF:

0.000664

Alfa

AF:

0.000695

Hom.:

Bravo

AF:

0.000480

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

May 09, 2020

- -

Familial aplasia of the vermis;C1510460:Orofaciodigital syndrome I

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 22, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

7.3

DANN

Benign

0.64

BranchPoint Hunter

1.0

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