chr5-42804013-T-C

Variant names:

• chr5-42804013-T-C
• rs13168440
• NM_005410.4:c.534+643A>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.534+643A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 152,232 control chromosomes in the GnomAD database, including 1,621 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 0.14 (1621 hom., cov: 33)
• Consequence: SELENOP NM_005410.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.771
• Publications: 14 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SELENOP	NM_005410.4	c.534+643A>G		intron_variant	Intron 4 of 4	ENST00000514985.6	NP_005401.3
SELENOP	NM_001093726.3	c.624+643A>G		intron_variant	Intron 5 of 5		NP_001087195.1
SELENOP	NM_001085486.3	c.534+643A>G		intron_variant	Intron 5 of 5		NP_001078955.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SELENOP	ENST00000514985.6	c.534+643A>G		intron_variant	Intron 4 of 4	1	NM_005410.4	ENSP00000420939.1

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20733 AN: 152114 Hom.: 1620 Cov.: 33

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.000967

Gnomad SAS AF: 0.0660

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.142

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.136 AC: 20736 AN: 152232 Hom.: 1621 Cov.: 33 AF XY: 0.137 AC XY: 10179 AN XY: 74430

African (AFR) AF: 0.100 AC: 4175 AN: 41546

American (AMR) AF: 0.120 AC: 1842 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.106 AC: 366 AN: 3468

East Asian (EAS) AF: 0.000969 AC: 5 AN: 5160

South Asian (SAS) AF: 0.0657 AC: 317 AN: 4828

European-Finnish (FIN) AF: 0.240 AC: 2544 AN: 10596

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.162 AC: 10991 AN: 68018

Other (OTH) AF: 0.141 AC: 298 AN: 2110

Alfa AF: 0.143 Hom.: 620

Bravo AF: 0.126

Asia WGS AF: 0.0320 AC: 112 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.6
DANN	Benign	0.44
PhyloP100		0.77
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: rs13168440; hg19: chr5-42804115;