16-56477824-T-C

Position:

• chr16-56477824-T-C

Variant summary

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

The NM_018233.4(OGFOD1):​c.*1619T>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 0.686 in 152,120 control chromosomes in the GnomAD database, including 37,639 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 (37638 hom., cov: 32)
  • Exomes 𝑓: 1.0 (1 hom.)
• Consequence: OGFOD1 NM_018233.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.109

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.914 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OGFOD1	NM_018233.4	c.*1619T>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.*1619T>C		3_prime_UTR_variant	13/13	1	NM_018233.4	ENSP00000457258.1
ENSG00000288725	ENST00000684388.1	n.1086+6937A>G		intron_variant				ENSP00000507647.1

Frequencies

GnomAD3 genomes AF: 0.686 AC: 104229 AN: 151998 Hom.: 37578 Cov.: 32

Gnomad AFR AF: 0.921

Gnomad AMI AF: 0.589

Gnomad AMR AF: 0.607

Gnomad ASJ AF: 0.582

Gnomad EAS AF: 0.597

Gnomad SAS AF: 0.740

Gnomad FIN AF: 0.474

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.604

Gnomad OTH AF: 0.655

GnomAD4 exome AF: 1.00 AC: 2 AN: 2 Hom.: 1 Cov.: 0 AF XY: 1.00 AC XY: 2 AN XY: 2

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.686 AC: 104338 AN: 152118 Hom.: 37638 Cov.: 32 AF XY: 0.679 AC XY: 50499 AN XY: 74370

Gnomad4 AFR AF: 0.922

Gnomad4 AMR AF: 0.607

Gnomad4 ASJ AF: 0.582

Gnomad4 EAS AF: 0.596

Gnomad4 SAS AF: 0.739

Gnomad4 FIN AF: 0.474

Gnomad4 NFE AF: 0.604

Gnomad4 OTH AF: 0.653

Alfa AF: 0.663 Hom.: 6224

Bravo AF: 0.705

Asia WGS AF: 0.715 AC: 2483 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	10
DANN	Benign	0.61

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: rs4783941; hg19: chr16-56511736;