rs180940027

chrX-13768700-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_003611.3(OFD1):c.2929-18C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0088 in 1,190,821 control chromosomes in the GnomAD database, including 45 homozygotes. There are 3,109 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 0.0060 (1 hom., 184 hem., cov: 23)
  • Exomes 𝑓: 0.0091 (44 hom. 2925 hem.)
• Consequence: OFD1 NM_003611.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -0.649

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant X-13768700-C-T is Benign according to our data. Variant chrX-13768700-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 259098.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-13768700-C-T is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00601 (672/111804) while in subpopulation NFE AF= 0.00974 (518/53157). AF 95% confidence interval is 0.00905. There are 1 homozygotes in gnomad4. There are 184 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.
• BS2: High Hemizygotes in GnomAd at 184 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OFD1	NM_003611.3	c.2929-18C>T		intron_variant		ENST00000340096.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OFD1	ENST00000340096.11	c.2929-18C>T		intron_variant		1	NM_003611.3	P1

Frequencies

GnomAD3 genomes AF: 0.00601 AC: 672 AN: 111752 Hom.: 1 Cov.: 23 AF XY: 0.00542 AC XY: 184 AN XY: 33940

Gnomad AFR AF: 0.00114

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00351

Gnomad ASJ AF: 0.00907

Gnomad EAS AF: 0.000278

Gnomad SAS AF: 0.00150

Gnomad FIN AF: 0.00621

Gnomad MID AF: 0.00420

Gnomad NFE AF: 0.00974

Gnomad OTH AF: 0.0100

GnomAD3 exomes AF: 0.00678 AC: 1239 AN: 182862 Hom.: 6 AF XY: 0.00710 AC XY: 478 AN XY: 67344

Gnomad AFR exome AF: 0.000913

Gnomad AMR exome AF: 0.00326

Gnomad ASJ exome AF: 0.0141

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00255

Gnomad FIN exome AF: 0.00550

Gnomad NFE exome AF: 0.0106

Gnomad OTH exome AF: 0.00687

GnomAD4 exome AF: 0.00909 AC: 9810 AN: 1079017 Hom.: 44 Cov.: 27 AF XY: 0.00843 AC XY: 2925 AN XY: 347021

Gnomad4 AFR exome AF: 0.00119

Gnomad4 AMR exome AF: 0.00387

Gnomad4 ASJ exome AF: 0.0132

Gnomad4 EAS exome AF: 0.0000332

Gnomad4 SAS exome AF: 0.00239

Gnomad4 FIN exome AF: 0.00555

Gnomad4 NFE exome AF: 0.0104

Gnomad4 OTH exome AF: 0.00933

GnomAD4 genome AF: 0.00601 AC: 672 AN: 111804 Hom.: 1 Cov.: 23 AF XY: 0.00541 AC XY: 184 AN XY: 34002

Gnomad4 AFR AF: 0.00114

Gnomad4 AMR AF: 0.00350

Gnomad4 ASJ AF: 0.00907

Gnomad4 EAS AF: 0.000279

Gnomad4 SAS AF: 0.00150

Gnomad4 FIN AF: 0.00621

Gnomad4 NFE AF: 0.00974

Gnomad4 OTH AF: 0.00988

Alfa AF: 0.00796 Hom.: 64

Bravo AF: 0.00569

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:6

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 06, 2016	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. -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Jun 20, 2017

- -

Familial aplasia of the vermis;C1510460:Orofaciodigital syndrome I Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 26, 2024

- -

Retinitis pigmentosa 23;C1510460:Orofaciodigital syndrome I;C1846175:Simpson-Golabi-Behmel syndrome type 2;C2749019:Joubert syndrome 10 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Jul 23, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.041
Dann	Benign	0.45

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

Other links and lift over

dbSNP: rs180940027; hg19: chrX-13786819;