16-56464599-G-T

Variant names:

• chr16-56464599-G-T
• rs4784670
• NM_018233.4:c.449-1553G>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.449-1553G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.687 in 151,880 control chromosomes in the GnomAD database, including 37,684 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 (37684 hom., cov: 31)
• Consequence: OGFOD1 NM_018233.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.216
• Publications: 12 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:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.917 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018233.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OGFOD1	NM_018233.4	MANE Select	c.449-1553G>T		intron	N/A	NP_060703.3
	OGFOD1	NM_001324357.2		c.446-1553G>T		intron	N/A	NP_001311286.1
	OGFOD1	NM_001324363.2		c.449-1553G>T		intron	N/A	NP_001311292.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OGFOD1	ENST00000566157.6	TSL:1 MANE Select	c.449-1553G>T		intron	N/A	ENSP00000457258.1	Q8N543-1
	ENSG00000288725	ENST00000684388.1		n.*1-16610C>A		intron	N/A	ENSP00000507647.1	A0A804HJU2
	OGFOD1	ENST00000924152.1		c.449-1553G>T		intron	N/A	ENSP00000594211.1

Frequencies

GnomAD3 genomes AF: 0.687 AC: 104189 AN: 151762 Hom.: 37623 Cov.: 31

Gnomad AFR AF: 0.925

Gnomad AMI AF: 0.588

Gnomad AMR AF: 0.608

Gnomad ASJ AF: 0.581

Gnomad EAS AF: 0.597

Gnomad SAS AF: 0.734

Gnomad FIN AF: 0.473

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.604

Gnomad OTH AF: 0.656

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.687 AC: 104299 AN: 151880 Hom.: 37684 Cov.: 31 AF XY: 0.680 AC XY: 50450 AN XY: 74212

African (AFR) AF: 0.925 AC: 38390 AN: 41500

American (AMR) AF: 0.607 AC: 9269 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.581 AC: 2013 AN: 3462

East Asian (EAS) AF: 0.596 AC: 3075 AN: 5156

South Asian (SAS) AF: 0.733 AC: 3528 AN: 4810

European-Finnish (FIN) AF: 0.473 AC: 4954 AN: 10468

Middle Eastern (MID) AF: 0.531 AC: 156 AN: 294

European-Non Finnish (NFE) AF: 0.604 AC: 40998 AN: 67906

Other (OTH) AF: 0.654 AC: 1381 AN: 2112

Alfa AF: 0.634 Hom.: 15387

Bravo AF: 0.706

Asia WGS AF: 0.714 AC: 2484 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.6
DANN	Benign	0.71
PhyloP100		0.22
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: rs4784670; hg19: chr16-56498511;