rs6413428

Positions:

• chr5-42800622-A-G

Variant summary

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

The NM_005410.4(SELENOP):​c.*98T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 1,378,504 control chromosomes in the GnomAD database, including 41,137 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 (5519 hom., cov: 33)
  • Exomes 𝑓: 0.23 (35618 hom.)
• Consequence: SELENOP NM_005410.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.702

Genes affected

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

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.341 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC152	NM_001134848.2	c.*841A>G		3_prime_UTR_variant	9/9	ENST00000361970.10
SELENOP	NM_005410.4	c.*98T>C		3_prime_UTR_variant	5/5	ENST00000514985.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC152	ENST00000361970.10	c.*841A>G		3_prime_UTR_variant	9/9	1	NM_001134848.2	P1
SELENOP	ENST00000514985.6	c.*98T>C		3_prime_UTR_variant	5/5	1	NM_005410.4	P1

Frequencies

GnomAD3 genomes AF: 0.257 AC: 39011 AN: 152042 Hom.: 5509 Cov.: 33

Gnomad AFR AF: 0.345

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.263

GnomAD4 exome AF: 0.233 AC: 285556 AN: 1226344 Hom.: 35618 Cov.: 17 AF XY: 0.231 AC XY: 139350 AN XY: 604482

Gnomad4 AFR exome AF: 0.349

Gnomad4 AMR exome AF: 0.154

Gnomad4 ASJ exome AF: 0.260

Gnomad4 EAS exome AF: 0.000343

Gnomad4 SAS exome AF: 0.130

Gnomad4 FIN exome AF: 0.288

Gnomad4 NFE exome AF: 0.245

Gnomad4 OTH exome AF: 0.235

GnomAD4 genome AF: 0.257 AC: 39050 AN: 152160 Hom.: 5519 Cov.: 33 AF XY: 0.252 AC XY: 18780 AN XY: 74416

Gnomad4 AFR AF: 0.345

Gnomad4 AMR AF: 0.193

Gnomad4 ASJ AF: 0.259

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.123

Gnomad4 FIN AF: 0.285

Gnomad4 NFE AF: 0.240

Gnomad4 OTH AF: 0.261

Alfa AF: 0.239 Hom.: 7519

Bravo AF: 0.256

Asia WGS AF: 0.0670 AC: 235 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	9.3
DANN	Benign	0.76

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: rs6413428; hg19: chr5-42800724;