chr5-42809617-A-C

Variant names:

• chr5-42809617-A-C
• rs28919891
• NM_005410.4:c.-13-1251T>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.-13-1251T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00175 in 166,016 control chromosomes in the GnomAD database, including 6 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 0.0019 (6 hom., cov: 32)
  • Exomes 𝑓: 0.000073 (0 hom.)
• Consequence: SELENOP NM_005410.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.731
• 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=-0.85).
• BA1: GnomAdExome4 highest subpopulation (AMR) allele frequency = 0.0833 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.-13-1251T>G		intron	N/A	NP_005401.3
	SELENOP	NM_001093726.3		c.77+1074T>G		intron	N/A	NP_001087195.1
	SELENOP	NM_001085486.3		c.-14+143T>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.-13-1251T>G		intron	N/A	ENSP00000420939.1	P49908
	SELENOP	ENST00000506577.5	TSL:1	c.-13-1251T>G		intron	N/A	ENSP00000425915.1	P49908
	SELENOP	ENST00000511224.5	TSL:1	c.-14+143T>G		intron	N/A	ENSP00000427671.1	P49908

Frequencies

GnomAD3 genomes AF: 0.00191 AC: 291 AN: 152198 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.000748

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0164

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: 0.0000882

Gnomad OTH AF: 0.00191

GnomAD4 exome AF: 0.0000730 AC: 1 AN: 13700 Hom.: 0 AF XY: 0.000149 AC XY: 1 AN XY: 6728

African (AFR) AF: 0.00 AC: 0 AN: 238

American (AMR) AF: 0.0833 AC: 1 AN: 12

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 94

East Asian (EAS) AF: 0.00 AC: 0 AN: 56

South Asian (SAS) AF: 0.00 AC: 0 AN: 248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 48

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 12570

Other (OTH) AF: 0.00 AC: 0 AN: 430

GnomAD4 genome AF: 0.00190 AC: 289 AN: 152316 Hom.: 6 Cov.: 32 AF XY: 0.00197 AC XY: 147 AN XY: 74494

African (AFR) AF: 0.000746 AC: 31 AN: 41582

American (AMR) AF: 0.0162 AC: 248 AN: 15302

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

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

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68016

Other (OTH) AF: 0.00189 AC: 4 AN: 2114

Alfa AF: 0.00189 Hom.: 0

Bravo AF: 0.00329

Asia WGS AF: 0.000289 AC: 1 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.2
DANN	Benign	0.77
PhyloP100		0.73
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: rs28919891; hg19: chr5-42809719;