Genetic Variant SELENOF:c.*849G>A (chr1-86862625-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_004261.5(SELENOF):c.*849G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 151,958 control chromosomes in the GnomAD database, including 6,290 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 0.26 ( 6290 hom., cov: 33)

Failed GnomAD Quality Control

Consequence

SELENOF
NM_004261.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.45

Publications

13 publications found

Variant links:

Genes affected

SELENOF (HGNC:17705): (selenoprotein F) The protein encoded by this gene belongs to the SEP15/selenoprotein M family. The exact function of this protein is not known; however, it has been found to associate with UDP-glucose:glycoprotein glucosyltransferase (UGTR), an endoplasmic reticulum(ER)-resident protein, which is involved in the quality control of protein folding. The association with UGTR retains this protein in the ER, where it may play a role in protein folding. It has also been suggested to have a role in cancer etiology. This protein is a selenoprotein, containing the rare amino acid selenocysteine (Sec). 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. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Nov 2016]

SELENOF 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=-0.98).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004261.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SELENOF	NM_004261.5	MANE Select	c.*849G>A	3_prime_UTR	Exon 5 of 5	NP_004252.2
SELENOF	NR_144512.1		n.1424G>A	non_coding_transcript_exon	Exon 5 of 5
SELENOF	NR_144513.1		n.1408G>A	non_coding_transcript_exon	Exon 5 of 5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SELENOF	ENST00000331835.10	TSL:1 MANE Select	c.*849G>A	3_prime_UTR	Exon 5 of 5	ENSP00000328729.6
SELENOF	ENST00000370554.5	TSL:1	c.*922G>A	downstream_gene	N/A	ENSP00000359585.2
SELENOF	ENST00000648872.1		n.*1064G>A	downstream_gene	N/A	ENSP00000497584.1

Frequencies

GnomAD3 genomes

AF:

0.259

AC:

39311

AN:

151840

Hom.:

6268

Cov.:

show subpopulations

Gnomad AFR

AF:

0.446

Gnomad AMI

AF:

0.177

Gnomad AMR

AF:

0.180

Gnomad ASJ

AF:

0.179

Gnomad EAS

AF:

0.0312

Gnomad SAS

AF:

0.170

Gnomad FIN

AF:

0.158

Gnomad MID

AF:

0.218

Gnomad NFE

AF:

0.208

Gnomad OTH

AF:

0.232

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.259

AC:

39389

AN:

151958

Hom.:

6290

Cov.:

AF XY:

0.252

AC XY:

18741

AN XY:

74310

show subpopulations

African (AFR)

AF:

0.447

AC:

18506

AN:

41432

American (AMR)

AF:

0.181

AC:

2758

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.179

AC:

621

AN:

3466

East Asian (EAS)

AF:

0.0315

AC:

163

AN:

5180

South Asian (SAS)

AF:

0.170

AC:

819

AN:

4820

European-Finnish (FIN)

AF:

0.158

AC:

1664

AN:

10510

Middle Eastern (MID)

AF:

0.214

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.208

AC:

14143

AN:

67968

Other (OTH)

AF:

0.233

AC:

491

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1428

2857

4285

5714

7142

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

392

784

1176

1568

1960

<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:

0.225

Hom.:

12428

Bravo

AF:

0.265

Asia WGS

AF:

0.164

AC:

567

AN:

3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

0.10

(source)

DANN

Benign

0.29

PhyloP100

-1.5

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over