rs14129

Positions:

• chr19-17228303-G-A
• chr19-17228303-G-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_024578.3(OCEL1):​c.666G>A​(p.Lys222=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 1,613,584 control chromosomes in the GnomAD database, including 18,429 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 0.17 (2685 hom., cov: 31)
  • Exomes 𝑓: 0.14 (15744 hom.)
• Consequence: OCEL1 NM_024578.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.746

Genes affected

OCEL1 (HGNC:26221): (occludin/ELL domain containing 1) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP7: Synonymous conserved (PhyloP=0.746 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OCEL1	NM_024578.3	c.666G>A	p.Lys222=	synonymous_variant	5/6	ENST00000215061.9
OCEL1	XM_006722899.5	c.666G>A	p.Lys222=	synonymous_variant	5/6
OCEL1	XM_047439441.1	c.*46G>A		3_prime_UTR_variant	4/4
OCEL1	XM_047439442.1	c.*2G>A		3_prime_UTR_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OCEL1	ENST00000215061.9	c.666G>A	p.Lys222=	synonymous_variant	5/6	1	NM_024578.3	A2

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26158 AN: 151900 Hom.: 2683 Cov.: 31

Gnomad AFR AF: 0.271

Gnomad AMI AF: 0.0615

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.236

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.0772

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.156

GnomAD3 exomes AF: 0.174 AC: 43653 AN: 251434 Hom.: 4955 AF XY: 0.167 AC XY: 22630 AN XY: 135890

Gnomad AFR exome AF: 0.274

Gnomad AMR exome AF: 0.332

Gnomad ASJ exome AF: 0.112

Gnomad EAS exome AF: 0.242

Gnomad SAS exome AF: 0.220

Gnomad FIN exome AF: 0.0755

Gnomad NFE exome AF: 0.113

Gnomad OTH exome AF: 0.144

GnomAD4 exome AF: 0.135 AC: 197875 AN: 1461566 Hom.: 15744 Cov.: 32 AF XY: 0.137 AC XY: 99536 AN XY: 727082

Gnomad4 AFR exome AF: 0.276

Gnomad4 AMR exome AF: 0.315

Gnomad4 ASJ exome AF: 0.105

Gnomad4 EAS exome AF: 0.223

Gnomad4 SAS exome AF: 0.220

Gnomad4 FIN exome AF: 0.0748

Gnomad4 NFE exome AF: 0.117

Gnomad4 OTH exome AF: 0.147

GnomAD4 genome AF: 0.172 AC: 26180 AN: 152018 Hom.: 2685 Cov.: 31 AF XY: 0.172 AC XY: 12780 AN XY: 74280

Gnomad4 AFR AF: 0.271

Gnomad4 AMR AF: 0.229

Gnomad4 ASJ AF: 0.103

Gnomad4 EAS AF: 0.237

Gnomad4 SAS AF: 0.218

Gnomad4 FIN AF: 0.0772

Gnomad4 NFE AF: 0.112

Gnomad4 OTH AF: 0.156

Alfa AF: 0.128 Hom.: 2705

Bravo AF: 0.192

Asia WGS AF: 0.235 AC: 818 AN: 3478

EpiCase AF: 0.121

EpiControl AF: 0.123

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.5
DANN	Benign	0.59
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: rs14129; hg19: chr19-17339112; COSMIC: COSV52244903; COSMIC: COSV52244903;