rs28919893

Variant names:

• chr5-42808430-C-T
• rs28919893
• NM_005410.4:c.-13-64G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005410.4(SELENOP):​c.-13-64G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00629 in 539,280 control chromosomes in the GnomAD database, including 102 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 0.017 (85 hom., cov: 31)
  • Exomes 𝑓: 0.0019 (17 hom.)
• Consequence: SELENOP NM_005410.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.791
• Publications: 1 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0591 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005410.4. 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
	SELENOP	NM_005410.4	MANE Select	c.-13-64G>A		intron	N/A	NP_005401.3
	SELENOP	NM_001093726.3		c.78-64G>A		intron	N/A	NP_001087195.1
	SELENOP	NM_001085486.3		c.-13-64G>A		intron	N/A	NP_001078955.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SELENOP	ENST00000514985.6	TSL:1 MANE Select	c.-13-64G>A		intron	N/A	ENSP00000420939.1
	SELENOP	ENST00000506577.5	TSL:1	c.-13-64G>A		intron	N/A	ENSP00000425915.1
	SELENOP	ENST00000511224.5	TSL:1	c.-13-64G>A		intron	N/A	ENSP00000427671.1

Frequencies

GnomAD3 genomes AF: 0.0174 AC: 2640 AN: 152064 Hom.: 85 Cov.: 31

Gnomad AFR AF: 0.0611

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00498

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.0120

GnomAD4 exome AF: 0.00192 AC: 742 AN: 387098 Hom.: 17 Cov.: 6 AF XY: 0.00162 AC XY: 316 AN XY: 194580

African (AFR) AF: 0.0600 AC: 585 AN: 9754

American (AMR) AF: 0.00367 AC: 29 AN: 7898

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10152

East Asian (EAS) AF: 0.00 AC: 0 AN: 23890

South Asian (SAS) AF: 0.000128 AC: 1 AN: 7824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 24960

Middle Eastern (MID) AF: 0.00374 AC: 6 AN: 1604

European-Non Finnish (NFE) AF: 0.0000393 AC: 11 AN: 280242

Other (OTH) AF: 0.00530 AC: 110 AN: 20774

GnomAD4 genome AF: 0.0174 AC: 2649 AN: 152182 Hom.: 85 Cov.: 31 AF XY: 0.0163 AC XY: 1211 AN XY: 74412

African (AFR) AF: 0.0611 AC: 2537 AN: 41510

American (AMR) AF: 0.00497 AC: 76 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68008

Other (OTH) AF: 0.0118 AC: 25 AN: 2114

Alfa AF: 0.0173 Hom.: 6

Bravo AF: 0.0203

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.6
DANN	Benign	0.50
PhyloP100		0.79
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs28919893; hg19: chr5-42808532;