dbSNP rs113388610: SELENOP:c.416+10T>C (chr5-42806886-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_005410.4(SELENOP):c.416+10T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00231 in 1,512,442 control chromosomes in the GnomAD database, including 72 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 35 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 37 hom. )

Consequence

SELENOP
NM_005410.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0900

Publications

0 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:

ENSG00000272234 (HGNC:):

ENSG00000272234 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 5-42806886-A-G is Benign according to our data. Variant chr5-42806886-A-G is described in ClinVar as Benign. ClinVar VariationId is 787815.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0124 (1885/152280) while in subpopulation AFR AF = 0.0432 (1794/41568). AF 95% confidence interval is 0.0415. There are 35 homozygotes in GnomAd4. There are 845 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 35 AR gene

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SELENOP	NM_005410.4	MANE Select	c.416+10T>C	intron	N/A	NP_005401.3
SELENOP	NM_001093726.3		c.506+10T>C	intron	N/A	NP_001087195.1
SELENOP	NM_001085486.3		c.416+10T>C	intron	N/A	NP_001078955.1	P49908

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SELENOP	ENST00000514985.6	TSL:1 MANE Select	c.416+10T>C	intron	N/A	ENSP00000420939.1	P49908
SELENOP	ENST00000506577.5	TSL:1	c.416+10T>C	intron	N/A	ENSP00000425915.1	P49908
SELENOP	ENST00000511224.5	TSL:1	c.416+10T>C	intron	N/A	ENSP00000427671.1	P49908

Frequencies

GnomAD3 genomes

AF:

0.0123

AC:

1878

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0431

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00452

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00813

GnomAD2 exomes

AF:

0.00328

AC:

794

AN:

241862

AF XY:

0.00240

show subpopulations

Gnomad AFR exome

AF:

0.0477

Gnomad AMR exome

AF:

0.00131

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000991

Gnomad OTH exome

AF:

0.00138

GnomAD4 exome

AF:

0.00118

AC:

1609

AN:

1360162

Hom.:

Cov.:

AF XY:

0.00106

AC XY:

721

AN XY:

677616

show subpopulations

African (AFR)

AF:

0.0435

AC:

1352

AN:

31060

American (AMR)

AF:

0.00184

AC:

AN:

41948

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24894

East Asian (EAS)

AF:

0.00

AC:

AN:

38746

South Asian (SAS)

AF:

0.000148

AC:

AN:

81250

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52510

Middle Eastern (MID)

AF:

0.000744

AC:

AN:

5378

European-Non Finnish (NFE)

AF:

0.0000292

AC:

AN:

1027820

Other (OTH)

AF:

0.00237

AC:

134

AN:

56556

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

142

214

285

356

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

160

200

<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:

0.0124

AC:

1885

AN:

152280

Hom.:

Cov.:

AF XY:

0.0113

AC XY:

845

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.0432

AC:

1794

AN:

41568

American (AMR)

AF:

0.00458

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.000207

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68004

Other (OTH)

AF:

0.00804

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

184

275

367

459

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

<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:

0.0155

Hom.:

Bravo

AF:

0.0145

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

6.0

(source)

DANN

Benign

0.62

PhyloP100

-0.090

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over