rs14306

Positions:

• chr16-56476387-A-C
• chr16-56476387-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018233.4(OGFOD1):​c.*182A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.634 in 426,540 control chromosomes in the GnomAD database, including 88,490 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.69 (37300 hom., cov: 26)
  • Exomes 𝑓: 0.61 (51190 hom.)
• Consequence: OGFOD1 NM_018233.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.863

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.917 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OGFOD1	NM_018233.4	c.*182A>C		3_prime_UTR_variant	13/13	ENST00000566157.6	NP_060703.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OGFOD1	ENST00000566157.6	c.*182A>C		3_prime_UTR_variant	13/13	1	NM_018233.4	ENSP00000457258	P1

Frequencies

GnomAD3 genomes AF: 0.686 AC: 103136 AN: 150412 Hom.: 37242 Cov.: 26

Gnomad AFR AF: 0.924

Gnomad AMI AF: 0.592

Gnomad AMR AF: 0.606

Gnomad ASJ AF: 0.582

Gnomad EAS AF: 0.597

Gnomad SAS AF: 0.736

Gnomad FIN AF: 0.466

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.604

Gnomad OTH AF: 0.655

GnomAD4 exome AF: 0.606 AC: 167333 AN: 276016 Hom.: 51190 Cov.: 4 AF XY: 0.609 AC XY: 85911 AN XY: 141104

Gnomad4 AFR exome AF: 0.914

Gnomad4 AMR exome AF: 0.602

Gnomad4 ASJ exome AF: 0.586

Gnomad4 EAS exome AF: 0.616

Gnomad4 SAS exome AF: 0.758

Gnomad4 FIN exome AF: 0.476

Gnomad4 NFE exome AF: 0.599

Gnomad4 OTH exome AF: 0.629

GnomAD4 genome AF: 0.686 AC: 103240 AN: 150524 Hom.: 37300 Cov.: 26 AF XY: 0.679 AC XY: 49838 AN XY: 73420

Gnomad4 AFR AF: 0.925

Gnomad4 AMR AF: 0.606

Gnomad4 ASJ AF: 0.582

Gnomad4 EAS AF: 0.596

Gnomad4 SAS AF: 0.735

Gnomad4 FIN AF: 0.466

Gnomad4 NFE AF: 0.604

Gnomad4 OTH AF: 0.653

Alfa AF: 0.606 Hom.: 23721

Bravo AF: 0.706

Asia WGS AF: 0.712 AC: 2473 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.30
DANN	Benign	0.40
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs14306; hg19: chr16-56510299;