rs12519443

Positions:

• chr5-42819819-T-C
• chr5-42819819-T-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000506577.5(SELENOP):​c.-14+5622A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 152,108 control chromosomes in the GnomAD database, including 4,529 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 0.22 (4529 hom., cov: 32)
• Consequence: SELENOP ENST00000506577.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.67

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.42819819T>C		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SELENOP	ENST00000506577.5	c.-14+5622A>G		intron_variant		1		ENSP00000425915.1
SELENOP	ENST00000514218.5	c.-13-11453A>G		intron_variant		5		ENSP00000421626.1
ENSG00000286271	ENST00000651306.1	n.377+2468T>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.217 AC: 32969 AN: 151990 Hom.: 4518 Cov.: 32

Gnomad AFR AF: 0.0517

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.346

Gnomad ASJ AF: 0.245

Gnomad EAS AF: 0.262

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.333

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.265

Gnomad OTH AF: 0.206

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

GnomAD4 genome AF: 0.217 AC: 33004 AN: 152108 Hom.: 4529 Cov.: 32 AF XY: 0.221 AC XY: 16461 AN XY: 74344

Gnomad4 AFR AF: 0.0515

Gnomad4 AMR AF: 0.346

Gnomad4 ASJ AF: 0.245

Gnomad4 EAS AF: 0.263

Gnomad4 SAS AF: 0.240

Gnomad4 FIN AF: 0.333

Gnomad4 NFE AF: 0.265

Gnomad4 OTH AF: 0.212

Alfa AF: 0.254 Hom.: 969

Bravo AF: 0.210

Asia WGS AF: 0.236 AC: 822 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	9.5
DANN	Benign	0.86

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs12519443; hg19: chr5-42819921;