rs28919926

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_005410.4(SELENOP):c.1102C>T(p.Arg368Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00281 in 1,611,622 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R368P) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0026 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0028 ( 26 hom. )

Consequence

SELENOP
NM_005410.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.703

Publications

13 publications found

Variant links:

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]

SELENOP links:

CCDC152 (HGNC:34438): (coiled-coil domain containing 152)

CCDC152 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0053276718).

BS1

Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.00283 (4129/1459392) while in subpopulation MID AF = 0.0217 (125/5750). AF 95% confidence interval is 0.0186. There are 26 homozygotes in GnomAdExome4. There are 2182 alleles in the male GnomAdExome4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SELENOP	NM_005410.4 link	c.1102C>T	p.Arg368Cys	missense_variant	Exon 5 of 5	ENST00000514985.6	NP_005401.3
CCDC152	NM_001134848.2 link	c.*983G>A		3_prime_UTR_variant	Exon 9 of 9	ENST00000361970.10	NP_001128320.1	Q4G0S7-1A0A024R043

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SELENOP	ENST00000514985.6 link	c.1102C>T	p.Arg368Cys	missense_variant	Exon 5 of 5	1	NM_005410.4	ENSP00000420939.1		P49908
CCDC152	ENST00000361970.10 link	c.*983G>A		3_prime_UTR_variant	Exon 9 of 9	1	NM_001134848.2	ENSP00000354888.5		Q4G0S7-1

Frequencies

GnomAD3 genomes

AF:

0.00260

AC:

395

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000604

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00229

Gnomad ASJ

AF:

0.00749

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00456

Gnomad FIN

AF:

0.00585

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00303

Gnomad OTH

AF:

0.00575

GnomAD2 exomes

AF:

0.00368

AC:

908

AN:

246600

AF XY:

0.00400

show subpopulations

Gnomad AFR exome

AF:

0.000323

Gnomad AMR exome

AF:

0.00334

Gnomad ASJ exome

AF:

0.00776

Gnomad EAS exome

AF:

0.000167

Gnomad FIN exome

AF:

0.00571

Gnomad NFE exome

AF:

0.00375

Gnomad OTH exome

AF:

0.00647

GnomAD4 exome

AF:

0.00283

AC:

4129

AN:

1459392

Hom.:

Cov.:

AF XY:

0.00301

AC XY:

2182

AN XY:

725460

show subpopulations

African (AFR)

AF:

0.000658

AC:

AN:

33442

American (AMR)

AF:

0.00338

AC:

151

AN:

44636

Ashkenazi Jewish (ASJ)

AF:

0.00640

AC:

167

AN:

26100

East Asian (EAS)

AF:

0.0000757

AC:

AN:

39614

South Asian (SAS)

AF:

0.00457

AC:

393

AN:

86034

European-Finnish (FIN)

AF:

0.00700

AC:

374

AN:

53394

Middle Eastern (MID)

AF:

0.0217

AC:

125

AN:

5750

European-Non Finnish (NFE)

AF:

0.00237

AC:

2626

AN:

1110122

Other (OTH)

AF:

0.00444

AC:

268

AN:

60300

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

214

428

642

856

1070

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

172

258

344

430

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00259

AC:

395

AN:

152230

Hom.:

Cov.:

AF XY:

0.00310

AC XY:

231

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.000602

AC:

AN:

41534

American (AMR)

AF:

0.00229

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00749

AC:

AN:

3472

East Asian (EAS)

AF:

0.000386

AC:

AN:

5178

South Asian (SAS)

AF:

0.00456

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00585

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00303

AC:

206

AN:

68020

Other (OTH)

AF:

0.00569

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00318

Hom.:

Bravo

AF:

0.00226

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.000258

AC:

ESP6500EA

AF:

0.00326

AC:

ExAC

AF:

0.00383

AC:

463

Asia WGS

AF:

0.00404

AC:

AN:

3478

EpiCase

AF:

0.00616

EpiControl

AF:

0.00522

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.038

T;T;T

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.63

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.51

.;.;T

MetaRNN

Benign

0.0053

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;N;N

PhyloP100

0.70

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.63

N;N;N

REVEL

Benign

0.080

Sift

Uncertain

0.0060

D;D;D

Sift4G

Benign

0.13

T;T;T

MVP

0.16

MPC

0.10

ClinPred

0.020

GERP RS

2.0

Varity_R

0.10

Mutation Taster

=100/0

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over