16-56476160-A-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_018233.4(OGFOD1):c.1584A>C(p.Pro528=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0111 in 1,613,410 control chromosomes in the GnomAD database, including 130 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0086 (11 hom., cov: 32)
  • Exomes 𝑓: 0.011 (119 hom.)
• Consequence: OGFOD1 NM_018233.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.409

Genes affected

OGFOD1 (HGNC:25585): (2-oxoglutarate and iron dependent oxygenase domain containing 1) Enables peptidyl-proline 3-dioxygenase activity. Involved in several processes, including peptidyl-proline hydroxylation; regulation of translational termination; and stress granule assembly. Located in cytoplasmic stress granule; cytosol; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

BBS2 (HGNC:967): (Bardet-Biedl syndrome 2) This gene is a member of the Bardet-Biedl syndrome (BBS) gene family. Bardet-Biedl syndrome is an autosomal recessive disorder characterized by severe pigmentary retinopathy, obesity, polydactyly, renal malformation and cognitive disability. The proteins encoded by BBS gene family members are structurally diverse and the similar phenotypes exhibited by mutations in BBS gene family members is likely due to their shared roles in cilia formation and function. Many BBS proteins localize to the basal bodies, ciliary axonemes, and pericentriolar regions of cells. BBS proteins may also be involved in intracellular trafficking via microtubule-related transport. The protein encoded by this gene forms a multiprotein BBSome complex with seven other BBS proteins.[provided by RefSeq, Oct 2014]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 16-56476160-A-C is Benign according to our data. Variant chr16-56476160-A-C is described in ClinVar as [Benign]. Clinvar id is 3024873.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.409 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00859 (1308/152330) while in subpopulation AMR AF= 0.0174 (266/15304). AF 95% confidence interval is 0.0157. There are 11 homozygotes in gnomad4. There are 651 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OGFOD1	NM_018233.4	c.1584A>C	p.Pro528=	synonymous_variant	13/13	ENST00000566157.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OGFOD1	ENST00000566157.6	c.1584A>C	p.Pro528=	synonymous_variant	13/13	1	NM_018233.4	P1

Frequencies

GnomAD3 genomes AF: 0.00859 AC: 1308 AN: 152212 Hom.: 11 Cov.: 32

Gnomad AFR AF: 0.00191

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0174

Gnomad ASJ AF: 0.0144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00414

Gnomad FIN AF: 0.00311

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0123

Gnomad OTH AF: 0.0115

GnomAD3 exomes AF: 0.00828 AC: 2078 AN: 251062 Hom.: 11 AF XY: 0.00878 AC XY: 1191 AN XY: 135688

Gnomad AFR exome AF: 0.00210

Gnomad AMR exome AF: 0.00784

Gnomad ASJ exome AF: 0.0131

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00422

Gnomad FIN exome AF: 0.00347

Gnomad NFE exome AF: 0.0122

Gnomad OTH exome AF: 0.00914

GnomAD4 exome AF: 0.0113 AC: 16536 AN: 1461080 Hom.: 119 Cov.: 31 AF XY: 0.0112 AC XY: 8174 AN XY: 726838

Gnomad4 AFR exome AF: 0.00194

Gnomad4 AMR exome AF: 0.00823

Gnomad4 ASJ exome AF: 0.0130

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00443

Gnomad4 FIN exome AF: 0.00393

Gnomad4 NFE exome AF: 0.0130

Gnomad4 OTH exome AF: 0.0103

GnomAD4 genome AF: 0.00859 AC: 1308 AN: 152330 Hom.: 11 Cov.: 32 AF XY: 0.00874 AC XY: 651 AN XY: 74490

Gnomad4 AFR AF: 0.00190

Gnomad4 AMR AF: 0.0174

Gnomad4 ASJ AF: 0.0144

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00414

Gnomad4 FIN AF: 0.00311

Gnomad4 NFE AF: 0.0123

Gnomad4 OTH AF: 0.0114

Alfa AF: 0.0112 Hom.: 9

Bravo AF: 0.00894

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.0138

EpiControl AF: 0.0134

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2024

BBS2: BS1, BS2; OGFOD1: BP4, BP7, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	8.7
Dann	Benign	0.77

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: rs61745416; hg19: chr16-56510072;