dbSNP rs3786777: SELENOW:c.*19-1384A>C (chr19-47782906-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003009.4(SELENOW):c.*19-1384A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 152,180 control chromosomes in the GnomAD database, including 13,894 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 0.38 ( 13878 hom., cov: 32)

Exomes 𝑓: 0.50 ( 16 hom. )

Consequence

SELENOW
NM_003009.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0470

Publications

20 publications found

Variant links:

Genes affected

SELENOW (HGNC:10752): (selenoprotein W) This gene encodes a selenoprotein containing a selenocysteine (Sec) residue, which is encoded by the UGA codon that normally signals translation termination. The 3' UTRs of selenoprotein mRNAs contain a conserved stem-loop structure, the Sec insertion sequence (SECIS) element that is necessary for the recognition of UGA as a Sec codon rather than as a stop signal. This protein is highly expressed in skeletal muscle, heart and brain. It belongs to the SelWTH family, which possesses a thioredoxin-like fold and a conserved CxxU (C is cysteine, U is Sec) motif, suggesting a redox function for this gene. Studies in mouse show that this selenoprotein is involved in muscle growth and differentiation, and in the protection of neurons from oxidative stress during neuronal development. A retroprocessed pseudogene of this locus has been identified on chromosome 1. [provided by RefSeq, Aug 2017]

SELENOW links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.563 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SELENOW	NM_003009.4 link	c.*19-1384A>C		intron_variant	Intron 5 of 5	ENST00000601048.6	NP_003000.1	P63302

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SELENOW	ENST00000601048.6 link	c.*19-1384A>C		intron_variant	Intron 5 of 5	1	NM_003009.4	ENSP00000473185.1		P63302

Frequencies

GnomAD3 genomes

AF:

0.385

AC:

58564

AN:

151978

Hom.:

13886

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0977

Gnomad AMI

AF:

0.431

Gnomad AMR

AF:

0.456

Gnomad ASJ

AF:

0.358

Gnomad EAS

AF:

0.400

Gnomad SAS

AF:

0.582

Gnomad FIN

AF:

0.527

Gnomad MID

AF:

0.306

Gnomad NFE

AF:

0.509

Gnomad OTH

AF:

0.372

GnomAD4 exome

AF:

0.500

AC:

AN:

Hom.:

Cov.:

AF XY:

0.516

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.333

AC:

AN:

South Asian (SAS)

AF:

1.00

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.534

AC:

AN:

Other (OTH)

AF:

0.625

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.560

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

AF:

0.385

AC:

58555

AN:

152096

Hom.:

13878

Cov.:

AF XY:

0.391

AC XY:

29074

AN XY:

74318

show subpopulations

African (AFR)

AF:

0.0974

AC:

4047

AN:

41538

American (AMR)

AF:

0.456

AC:

6957

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.358

AC:

1241

AN:

3468

East Asian (EAS)

AF:

0.399

AC:

2065

AN:

5172

South Asian (SAS)

AF:

0.581

AC:

2801

AN:

4822

European-Finnish (FIN)

AF:

0.527

AC:

5564

AN:

10556

Middle Eastern (MID)

AF:

0.312

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.509

AC:

34613

AN:

67970

Other (OTH)

AF:

0.372

AC:

785

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1596

3192

4789

6385

7981

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

550

1100

1650

2200

2750

<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:

0.466

Hom.:

55571

Bravo

AF:

0.361

Asia WGS

AF:

0.479

AC:

1668

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.92

(source)

DANN

Benign

0.40

PhyloP100

-0.047

Mutation Taster

=100/0

polymorphism (auto)

(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