rs230820

Variant names:

• chr5-42807322-A-C
• rs230820
• NM_005410.4:c.204-214T>G

Your query was ambiguous. Multiple possible variants found:

• chr5-42807322-A-C
• chr5-42807322-A-T

Variant summary

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

The NM_005410.4(SELENOP):​c.204-214T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.546 in 331,824 control chromosomes in the GnomAD database, including 49,993 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 0.55 (23406 hom., cov: 32)
  • Exomes 𝑓: 0.54 (26587 hom.)
• Consequence: SELENOP NM_005410.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.57
• Publications: 9 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.589 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SELENOP	NM_005410.4	MANE Select	c.204-214T>G		intron	N/A	NP_005401.3
	SELENOP	NM_001093726.3		c.294-214T>G		intron	N/A	NP_001087195.1
	SELENOP	NM_001085486.3		c.204-214T>G		intron	N/A	NP_001078955.1	P49908

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SELENOP	ENST00000514985.6	TSL:1 MANE Select	c.204-214T>G		intron	N/A	ENSP00000420939.1	P49908
	SELENOP	ENST00000506577.5	TSL:1	c.204-214T>G		intron	N/A	ENSP00000425915.1	P49908
	SELENOP	ENST00000511224.5	TSL:1	c.204-214T>G		intron	N/A	ENSP00000427671.1	P49908

Frequencies

GnomAD3 genomes AF: 0.552 AC: 83872 AN: 151828 Hom.: 23357 Cov.: 32

Gnomad AFR AF: 0.553

Gnomad AMI AF: 0.638

Gnomad AMR AF: 0.599

Gnomad ASJ AF: 0.548

Gnomad EAS AF: 0.419

Gnomad SAS AF: 0.525

Gnomad FIN AF: 0.636

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.541

Gnomad OTH AF: 0.547

GnomAD4 exome AF: 0.540 AC: 97071 AN: 179878 Hom.: 26587 Cov.: 2 AF XY: 0.538 AC XY: 49364 AN XY: 91794

African (AFR) AF: 0.562 AC: 4249 AN: 7558

American (AMR) AF: 0.623 AC: 5067 AN: 8130

Ashkenazi Jewish (ASJ) AF: 0.556 AC: 3634 AN: 6536

East Asian (EAS) AF: 0.423 AC: 6914 AN: 16346

South Asian (SAS) AF: 0.523 AC: 5805 AN: 11106

European-Finnish (FIN) AF: 0.629 AC: 4635 AN: 7366

Middle Eastern (MID) AF: 0.462 AC: 381 AN: 824

European-Non Finnish (NFE) AF: 0.544 AC: 60239 AN: 110760

Other (OTH) AF: 0.546 AC: 6147 AN: 11252

GnomAD4 genome AF: 0.553 AC: 83993 AN: 151946 Hom.: 23406 Cov.: 32 AF XY: 0.553 AC XY: 41055 AN XY: 74272

African (AFR) AF: 0.554 AC: 22958 AN: 41448

American (AMR) AF: 0.599 AC: 9142 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.548 AC: 1899 AN: 3464

East Asian (EAS) AF: 0.419 AC: 2165 AN: 5164

South Asian (SAS) AF: 0.524 AC: 2529 AN: 4824

European-Finnish (FIN) AF: 0.636 AC: 6719 AN: 10560

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.541 AC: 36717 AN: 67920

Other (OTH) AF: 0.549 AC: 1155 AN: 2104

Alfa AF: 0.425 Hom.: 1197

Bravo AF: 0.550

Asia WGS AF: 0.462 AC: 1602 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.41
DANN	Benign	0.43
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

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: rs230820; hg19: chr5-42807424;