rs4838862

Positions:

• chr22-50205200-G-A
• chr22-50205200-G-C

Variant summary

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

The NM_031454.2(SELENOO):​c.555-1117G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.39 (4546 hom., cov: 0)
• Consequence: SELENOO NM_031454.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.75

Genes affected

SELENOO (HGNC:30395): (selenoprotein O) This gene encodes a selenoprotein that is localized to the mitochondria. It is the largest mammalian selenoprotein, containing the rare amino acid selenocysteine (Sec). Sec is encoded by the UGA codon, which normally signals translation termination. The 3' UTRs of selenoprotein mRNAs contain a conserved stem-loop structure, designated the Sec insertion sequence (SECIS) element, that is necessary for the recognition of UGA as a Sec codon, rather than as a stop signal. The exact function of this selenoprotein is not known, but it is thought to have redox activity. [provided by RefSeq, Dec 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SELENOO	NM_031454.2	c.555-1117G>A		intron_variant		ENST00000380903.7	NP_113642.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SELENOO	ENST00000380903.7	c.555-1117G>A		intron_variant		1	NM_031454.2	ENSP00000370288.2

Frequencies

GnomAD3 genomes AF: 0.389 AC: 24937 AN: 64114 Hom.: 4539 Cov.: 0

Gnomad AFR AF: 0.482

Gnomad AMI AF: 0.367

Gnomad AMR AF: 0.338

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.348

Gnomad SAS AF: 0.486

Gnomad FIN AF: 0.420

Gnomad MID AF: 0.287

Gnomad NFE AF: 0.358

Gnomad OTH AF: 0.349

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

GnomAD4 genome AF: 0.389 AC: 24961 AN: 64158 Hom.: 4546 Cov.: 0 AF XY: 0.398 AC XY: 12690 AN XY: 31906

Gnomad4 AFR AF: 0.483

Gnomad4 AMR AF: 0.338

Gnomad4 ASJ AF: 0.292

Gnomad4 EAS AF: 0.348

Gnomad4 SAS AF: 0.487

Gnomad4 FIN AF: 0.420

Gnomad4 NFE AF: 0.358

Gnomad4 OTH AF: 0.346

Alfa AF: 0.516 Hom.: 2626

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.33
DANN	Benign	0.89

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: rs4838862; hg19: chr22-50643629; COSMIC: COSV66599453; COSMIC: COSV66599453;