16-56477824-T-C

Variant names:

• chr16-56477824-T-C
• rs4783941
• NM_018233.4:c.*1619T>C

Variant summary

Our verdict is Benign. The variant received -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
• 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:):

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: Ambry Genetics, G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Myriad Women’s Health
• BBS2-related 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.914 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.*1619T>C		3_prime_UTR	Exon 13 of 13	NP_060703.3
	OGFOD1	NM_001324357.2		c.*1619T>C		3_prime_UTR	Exon 13 of 13	NP_001311286.1
	OGFOD1	NM_001324363.2		c.*1619T>C		3_prime_UTR	Exon 12 of 12	NP_001311292.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OGFOD1	ENST00000566157.6	TSL:1 MANE Select	c.*1619T>C		3_prime_UTR	Exon 13 of 13	ENSP00000457258.1	Q8N543-1
	ENSG00000288725	ENST00000684388.1		n.1086+6937A>G		intron	N/A	ENSP00000507647.1	A0A804HJU2
	BBS2	ENST00000682047.1		c.2166+6937A>G		intron	N/A	ENSP00000507699.1	Q9BXC9

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AF: 1.00 AC: 2 AN: 2

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

African (AFR) AF: 0.922 AC: 38270 AN: 41528

American (AMR) AF: 0.607 AC: 9277 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.582 AC: 2017 AN: 3468

East Asian (EAS) AF: 0.596 AC: 3079 AN: 5164

South Asian (SAS) AF: 0.739 AC: 3560 AN: 4818

European-Finnish (FIN) AF: 0.474 AC: 4998 AN: 10554

Middle Eastern (MID) AF: 0.534 AC: 157 AN: 294

European-Non Finnish (NFE) AF: 0.604 AC: 41064 AN: 67976

Other (OTH) AF: 0.653 AC: 1380 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	10
DANN	Benign	0.61
PhyloP100		-0.11
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: rs4783941; hg19: chr16-56511736;