rs230819

Variant names:

• chr5-42805863-C-A
• rs230819
• NM_005410.4:c.416+1033G>T

Your query was ambiguous. Multiple possible variants found:

• chr5-42805863-C-A
• chr5-42805863-C-G

Variant summary

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

The NM_005410.4(SELENOP):​c.416+1033G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.506 in 151,930 control chromosomes in the GnomAD database, including 19,653 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 0.51 (19653 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: SELENOP NM_005410.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.930
• Publications: 22 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.549 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.416+1033G>T		intron	N/A	NP_005401.3
	SELENOP	NM_001093726.3		c.506+1033G>T		intron	N/A	NP_001087195.1
	SELENOP	NM_001085486.3		c.416+1033G>T		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.416+1033G>T		intron	N/A	ENSP00000420939.1	P49908
	SELENOP	ENST00000506577.5	TSL:1	c.416+1033G>T		intron	N/A	ENSP00000425915.1	P49908
	SELENOP	ENST00000511224.5	TSL:1	c.416+1033G>T		intron	N/A	ENSP00000427671.1	P49908

Frequencies

GnomAD3 genomes AF: 0.505 AC: 76683 AN: 151812 Hom.: 19599 Cov.: 33

Gnomad AFR AF: 0.537

Gnomad AMI AF: 0.593

Gnomad AMR AF: 0.558

Gnomad ASJ AF: 0.401

Gnomad EAS AF: 0.420

Gnomad SAS AF: 0.481

Gnomad FIN AF: 0.594

Gnomad MID AF: 0.325

Gnomad NFE AF: 0.474

Gnomad OTH AF: 0.483

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.506 AC: 76811 AN: 151930 Hom.: 19653 Cov.: 33 AF XY: 0.507 AC XY: 37668 AN XY: 74252

African (AFR) AF: 0.537 AC: 22252 AN: 41400

American (AMR) AF: 0.558 AC: 8536 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.401 AC: 1389 AN: 3468

East Asian (EAS) AF: 0.421 AC: 2173 AN: 5166

South Asian (SAS) AF: 0.481 AC: 2320 AN: 4826

European-Finnish (FIN) AF: 0.594 AC: 6259 AN: 10544

Middle Eastern (MID) AF: 0.336 AC: 98 AN: 292

European-Non Finnish (NFE) AF: 0.474 AC: 32221 AN: 67932

Other (OTH) AF: 0.486 AC: 1025 AN: 2110

Alfa AF: 0.471 Hom.: 9926

Bravo AF: 0.502

Asia WGS AF: 0.443 AC: 1538 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.13
DANN	Benign	0.094
PhyloP100		-0.93
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: rs230819; hg19: chr5-42805965;