rs230820

Positions:

• chr5-42807322-A-C
• chr5-42807322-A-T

Variant summary

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

The NM_005410.4(SELENOP):​c.204-214T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.546 in 331,824 control chromosomes in the GnomAD database, including 49,993 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 0.55 (23406 hom., cov: 32)
  • Exomes 𝑓: 0.54 (26587 hom.)
• Consequence: SELENOP NM_005410.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.57

Genes affected

SELENOP (HGNC:10751): (selenoprotein P) This gene encodes a selenoprotein that is predominantly expressed in the liver and secreted into the plasma. This selenoprotein is unique in that it contains multiple selenocysteine (Sec) residues per polypeptide (10 in human), and accounts for most of the selenium in plasma. It has been implicated as an extracellular antioxidant, and in the transport of selenium to extra-hepatic tissues via apolipoprotein E receptor-2 (apoER2). Mice lacking this gene exhibit neurological dysfunction, suggesting its importance in normal brain function. 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 mRNA for this selenoprotein contains two SECIS elements. The use of alternative polyadenylation sites, one located in between the two SECIS elements, results in two populations of mRNAs containing either both (predominant) or just the upstream SECIS element (PMID:27881738). Alternatively spliced transcript variants have also been found for this gene. [provided by RefSeq, Oct 2018]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.589 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SELENOP	NM_005410.4	c.204-214T>G		intron_variant		ENST00000514985.6	NP_005401.3
SELENOP	NM_001085486.3	c.204-214T>G		intron_variant			NP_001078955.1
SELENOP	NM_001093726.3	c.294-214T>G		intron_variant			NP_001087195.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SELENOP	ENST00000514985.6	c.204-214T>G		intron_variant		1	NM_005410.4	ENSP00000420939	P1

Frequencies

GnomAD3 genomes AF: 0.552 AC: 83872 AN: 151828 Hom.: 23357 Cov.: 32

Gnomad AFR AF: 0.553

Gnomad AMI AF: 0.638

Gnomad AMR AF: 0.599

Gnomad ASJ AF: 0.548

Gnomad EAS AF: 0.419

Gnomad SAS AF: 0.525

Gnomad FIN AF: 0.636

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.541

Gnomad OTH AF: 0.547

GnomAD4 exome AF: 0.540 AC: 97071 AN: 179878 Hom.: 26587 Cov.: 2 AF XY: 0.538 AC XY: 49364 AN XY: 91794

Gnomad4 AFR exome AF: 0.562

Gnomad4 AMR exome AF: 0.623

Gnomad4 ASJ exome AF: 0.556

Gnomad4 EAS exome AF: 0.423

Gnomad4 SAS exome AF: 0.523

Gnomad4 FIN exome AF: 0.629

Gnomad4 NFE exome AF: 0.544

Gnomad4 OTH exome AF: 0.546

GnomAD4 genome AF: 0.553 AC: 83993 AN: 151946 Hom.: 23406 Cov.: 32 AF XY: 0.553 AC XY: 41055 AN XY: 74272

Gnomad4 AFR AF: 0.554

Gnomad4 AMR AF: 0.599

Gnomad4 ASJ AF: 0.548

Gnomad4 EAS AF: 0.419

Gnomad4 SAS AF: 0.524

Gnomad4 FIN AF: 0.636

Gnomad4 NFE AF: 0.541

Gnomad4 OTH AF: 0.549

Alfa AF: 0.415 Hom.: 1088

Bravo AF: 0.550

Asia WGS AF: 0.462 AC: 1602 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.41
DANN	Benign	0.43

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: rs230820; hg19: chr5-42807424;