rs14306

Variant names:

• chr16-56476387-A-C
• rs14306
• NM_018233.4:c.*182A>C

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 20 publications found

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]

ENSG00000288725 (HGNC:):

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]

BBS2 Gene-Disease associations (from GenCC):

• Bardet-Biedl syndrome 2

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Myriad Women’s Health
• ciliopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• retinitis pigmentosa 74

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Bardet-Biedl syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
OGFOD1	NM_018233.4	c.*182A>C		3_prime_UTR_variant	Exon 13 of 13	ENST00000566157.6	NP_060703.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OGFOD1	ENST00000566157.6	c.*182A>C		3_prime_UTR_variant	Exon 13 of 13	1	NM_018233.4	ENSP00000457258.1
ENSG00000288725	ENST00000684388.1	n.1086+8374T>G		intron_variant	Intron 8 of 13			ENSP00000507647.1

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

African (AFR) AF: 0.914 AC: 6799 AN: 7440

American (AMR) AF: 0.602 AC: 5088 AN: 8452

Ashkenazi Jewish (ASJ) AF: 0.586 AC: 5593 AN: 9544

East Asian (EAS) AF: 0.616 AC: 13625 AN: 22110

South Asian (SAS) AF: 0.758 AC: 7026 AN: 9268

European-Finnish (FIN) AF: 0.476 AC: 9968 AN: 20936

Middle Eastern (MID) AF: 0.598 AC: 811 AN: 1356

European-Non Finnish (NFE) AF: 0.599 AC: 107370 AN: 179338

Other (OTH) AF: 0.629 AC: 11053 AN: 17572

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

African (AFR) AF: 0.925 AC: 37940 AN: 41034

American (AMR) AF: 0.606 AC: 9170 AN: 15128

Ashkenazi Jewish (ASJ) AF: 0.582 AC: 2012 AN: 3458

East Asian (EAS) AF: 0.596 AC: 3048 AN: 5116

South Asian (SAS) AF: 0.735 AC: 3469 AN: 4720

European-Finnish (FIN) AF: 0.466 AC: 4716 AN: 10130

Middle Eastern (MID) AF: 0.531 AC: 154 AN: 290

European-Non Finnish (NFE) AF: 0.604 AC: 40832 AN: 67654

Other (OTH) AF: 0.653 AC: 1364 AN: 2090

Alfa AF: 0.633 Hom.: 72153

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
PhyloP100		-0.86
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs14306; hg19: chr16-56510299;