5-42800706-C-T

Position:

• chr5-42800706-C-T

Variant summary

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

The NM_005410.4(SELENOP):​c.*14G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 1,579,408 control chromosomes in the GnomAD database, including 69,443 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 0.26 (5715 hom., cov: 32)
  • Exomes 𝑓: 0.29 (63728 hom.)
• Consequence: SELENOP NM_005410.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.435

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]

CCDC152 (HGNC:34438): (coiled-coil domain containing 152)

SELENOP (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SELENOP	NM_005410.4	c.*14G>A		3_prime_UTR_variant	5/5	ENST00000514985.6	NP_005401.3
CCDC152	NM_001134848.2	c.*925C>T		3_prime_UTR_variant	9/9	ENST00000361970.10	NP_001128320.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SELENOP	ENST00000514985	c.*14G>A		3_prime_UTR_variant	5/5	1	NM_005410.4	ENSP00000420939.1
CCDC152	ENST00000361970.10	c.*925C>T		3_prime_UTR_variant	9/9	1	NM_001134848.2	ENSP00000354888.5

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39402 AN: 151954 Hom.: 5705 Cov.: 32

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.380

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.279

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.348

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.251

GnomAD3 exomes AF: 0.306 AC: 70631 AN: 231178 Hom.: 12049 AF XY: 0.297 AC XY: 37260 AN XY: 125264

Gnomad AFR exome AF: 0.136

Gnomad AMR exome AF: 0.498

Gnomad ASJ exome AF: 0.284

Gnomad EAS exome AF: 0.263

Gnomad SAS exome AF: 0.230

Gnomad FIN exome AF: 0.346

Gnomad NFE exome AF: 0.294

Gnomad OTH exome AF: 0.280

GnomAD4 exome AF: 0.294 AC: 419522 AN: 1427336 Hom.: 63728 Cov.: 32 AF XY: 0.292 AC XY: 205646 AN XY: 705358

Gnomad4 AFR exome AF: 0.135

Gnomad4 AMR exome AF: 0.478

Gnomad4 ASJ exome AF: 0.286

Gnomad4 EAS exome AF: 0.320

Gnomad4 SAS exome AF: 0.236

Gnomad4 FIN exome AF: 0.345

Gnomad4 NFE exome AF: 0.294

Gnomad4 OTH exome AF: 0.271

GnomAD4 genome AF: 0.259 AC: 39444 AN: 152072 Hom.: 5715 Cov.: 32 AF XY: 0.262 AC XY: 19464 AN XY: 74330

Gnomad4 AFR AF: 0.140

Gnomad4 AMR AF: 0.380

Gnomad4 ASJ AF: 0.281

Gnomad4 EAS AF: 0.280

Gnomad4 SAS AF: 0.227

Gnomad4 FIN AF: 0.348

Gnomad4 NFE AF: 0.291

Gnomad4 OTH AF: 0.256

Alfa AF: 0.286 Hom.: 6838

Bravo AF: 0.256

Asia WGS AF: 0.240 AC: 835 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.5
DANN	Benign	0.47

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: rs7579; hg19: chr5-42800808; COSMIC: COSV62792213; COSMIC: COSV62792213;