rs16872779

Variant names:

• chr5-42804935-G-A
• rs16872779
• NM_005410.4:c.417-162C>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.417-162C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00809 in 466,498 control chromosomes in the GnomAD database, including 161 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 0.0068 (50 hom., cov: 33)
  • Exomes 𝑓: 0.0087 (111 hom.)
• Consequence: SELENOP NM_005410.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.337
• Publications: 2 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.118 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.417-162C>T		intron	N/A	NP_005401.3
	SELENOP	NM_001093726.3		c.507-162C>T		intron	N/A	NP_001087195.1
	SELENOP	NM_001085486.3		c.417-162C>T		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.417-162C>T		intron	N/A	ENSP00000420939.1
	SELENOP	ENST00000506577.5	TSL:1	c.417-162C>T		intron	N/A	ENSP00000425915.1
	SELENOP	ENST00000511224.5	TSL:1	c.417-162C>T		intron	N/A	ENSP00000427671.1

Frequencies

GnomAD3 genomes AF: 0.00680 AC: 1034 AN: 152104 Hom.: 48 Cov.: 33

Gnomad AFR AF: 0.00234

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0108

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.0197

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00911

GnomAD4 exome AF: 0.00870 AC: 2734 AN: 314276 Hom.: 111 Cov.: 4 AF XY: 0.00896 AC XY: 1470 AN XY: 163998

African (AFR) AF: 0.00156 AC: 13 AN: 8354

American (AMR) AF: 0.0148 AC: 151 AN: 10234

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10284

East Asian (EAS) AF: 0.0782 AC: 1946 AN: 24900

South Asian (SAS) AF: 0.0209 AC: 317 AN: 15168

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30532

Middle Eastern (MID) AF: 0.000854 AC: 2 AN: 2342

European-Non Finnish (NFE) AF: 0.000145 AC: 28 AN: 193336

Other (OTH) AF: 0.0145 AC: 277 AN: 19126

GnomAD4 genome AF: 0.00682 AC: 1038 AN: 152222 Hom.: 50 Cov.: 33 AF XY: 0.00752 AC XY: 560 AN XY: 74420

African (AFR) AF: 0.00234 AC: 97 AN: 41538

American (AMR) AF: 0.0113 AC: 173 AN: 15286

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

East Asian (EAS) AF: 0.126 AC: 651 AN: 5184

South Asian (SAS) AF: 0.0195 AC: 94 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10584

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

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68022

Other (OTH) AF: 0.00949 AC: 20 AN: 2108

Alfa AF: 0.00290 Hom.: 1

Bravo AF: 0.00833

Asia WGS AF: 0.0660 AC: 230 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.6
DANN	Benign	0.45
PhyloP100		0.34
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: rs16872779; hg19: chr5-42805037; COSMIC: COSV62792033; COSMIC: COSV62792033;