5-42819819-T-C

Variant names:

• chr5-42819819-T-C
• rs12519443
• ENST00000506577.5:c.-14+5622A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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]

ENSG00000286271 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000506577.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SELENOP	ENST00000506577.5	TSL:1	c.-14+5622A>G		intron	N/A	ENSP00000425915.1
	SELENOP	ENST00000514218.5	TSL:5	c.-13-11453A>G		intron	N/A	ENSP00000421626.1
	ENSG00000286271	ENST00000651306.1		n.377+2468T>C		intron	N/A

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

African (AFR) AF: 0.0515 AC: 2140 AN: 41530

American (AMR) AF: 0.346 AC: 5289 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.245 AC: 847 AN: 3464

East Asian (EAS) AF: 0.263 AC: 1361 AN: 5176

South Asian (SAS) AF: 0.240 AC: 1158 AN: 4820

European-Finnish (FIN) AF: 0.333 AC: 3515 AN: 10560

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.265 AC: 18005 AN: 67966

Other (OTH) AF: 0.212 AC: 446 AN: 2106

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	9.5
DANN	Benign	0.86
PhyloP100		1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs12519443; hg19: chr5-42819921;