rs230819

chr5-42805863-C-Achr5-42805863-C-G

Variant summary

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

The NM_005410.4(SELENOP):c.416+1033G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.506 in 151,930 control chromosomes in the GnomAD database, including 19,653 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 0.51 (19653 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: SELENOP NM_005410.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.930

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.549 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SELENOP	NM_005410.4	c.416+1033G>T		intron_variant		ENST00000514985.6
SELENOP	NM_001085486.3	c.416+1033G>T		intron_variant
SELENOP	NM_001093726.3	c.506+1033G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SELENOP	ENST00000514985.6	c.416+1033G>T		intron_variant		1	NM_005410.4	P1

Frequencies

GnomAD3 genomes AF: 0.505 AC: 76683 AN: 151812 Hom.: 19599 Cov.: 33

Gnomad AFR AF: 0.537

Gnomad AMI AF: 0.593

Gnomad AMR AF: 0.558

Gnomad ASJ AF: 0.401

Gnomad EAS AF: 0.420

Gnomad SAS AF: 0.481

Gnomad FIN AF: 0.594

Gnomad MID AF: 0.325

Gnomad NFE AF: 0.474

Gnomad OTH AF: 0.483

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.506 AC: 76811 AN: 151930 Hom.: 19653 Cov.: 33 AF XY: 0.507 AC XY: 37668 AN XY: 74252

Gnomad4 AFR AF: 0.537

Gnomad4 AMR AF: 0.558

Gnomad4 ASJ AF: 0.401

Gnomad4 EAS AF: 0.421

Gnomad4 SAS AF: 0.481

Gnomad4 FIN AF: 0.594

Gnomad4 NFE AF: 0.474

Gnomad4 OTH AF: 0.486

Alfa AF: 0.459 Hom.: 6768

Bravo AF: 0.502

Asia WGS AF: 0.443 AC: 1538 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.13
Dann	Benign	0.094

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: rs230819; hg19: chr5-42805965;