chr22-50205200-G-A

Variant names:

• chr22-50205200-G-A
• rs4838862
• NM_031454.2:c.555-1117G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SELENOO	NM_031454.2	c.555-1117G>A		intron_variant	Intron 1 of 8	ENST00000380903.7	NP_113642.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SELENOO	ENST00000380903.7	c.555-1117G>A		intron_variant	Intron 1 of 8	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

African (AFR) AF: 0.483 AC: 6933 AN: 14368

American (AMR) AF: 0.338 AC: 2456 AN: 7272

Ashkenazi Jewish (ASJ) AF: 0.292 AC: 528 AN: 1810

East Asian (EAS) AF: 0.348 AC: 967 AN: 2776

South Asian (SAS) AF: 0.487 AC: 922 AN: 1894

European-Finnish (FIN) AF: 0.420 AC: 1838 AN: 4380

Middle Eastern (MID) AF: 0.293 AC: 41 AN: 140

European-Non Finnish (NFE) AF: 0.358 AC: 10765 AN: 30068

Other (OTH) AF: 0.346 AC: 343 AN: 992

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
PhyloP100		-1.8
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: rs4838862; hg19: chr22-50643629; COSMIC: COSV66599453; COSMIC: COSV66599453;