rs5859

chr1-86862842-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004261.5(SELENOF):c.*632G>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 0.306 in 152,382 control chromosomes in the GnomAD database, including 9,394 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 0.31 (9390 hom., cov: 33)
  • Exomes 𝑓: 0.22 (4 hom.)
• Consequence: SELENOF NM_004261.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.628

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.571 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SELENOF	NM_004261.5	c.*632G>A		3_prime_UTR_variant	5/5	ENST00000331835.10
SELENOF	NM_203341.3	c.*705G>A		3_prime_UTR_variant	4/4
SELENOF	NR_144512.1	n.1207G>A		non_coding_transcript_exon_variant	5/5
SELENOF	NR_144513.1	n.1191G>A		non_coding_transcript_exon_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SELENOF	ENST00000331835.10	c.*632G>A		3_prime_UTR_variant	5/5	1	NM_004261.5	P1
SELENOF	ENST00000370554.5	c.*705G>A		3_prime_UTR_variant	4/4	1
SELENOF	ENST00000648872.1	c.*847G>A		3_prime_UTR_variant, NMD_transcript_variant	6/6

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46409 AN: 151930 Hom.: 9366 Cov.: 33

Gnomad AFR AF: 0.577

Gnomad AMI AF: 0.180

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.0312

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.208

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.267

GnomAD4 exome AF: 0.222 AC: 74 AN: 334 Hom.: 4 Cov.: 0 AF XY: 0.227 AC XY: 45 AN XY: 198

Gnomad4 FIN exome AF: 0.212

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.306 AC: 46498 AN: 152048 Hom.: 9390 Cov.: 33 AF XY: 0.299 AC XY: 22210 AN XY: 74330

Gnomad4 AFR AF: 0.577

Gnomad4 AMR AF: 0.197

Gnomad4 ASJ AF: 0.182

Gnomad4 EAS AF: 0.0314

Gnomad4 SAS AF: 0.183

Gnomad4 FIN AF: 0.208

Gnomad4 NFE AF: 0.219

Gnomad4 OTH AF: 0.268

Alfa AF: 0.285 Hom.: 932

Bravo AF: 0.313

Asia WGS AF: 0.180 AC: 628 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
Cadd	Benign	10
Dann	Benign	0.71

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

LitVar

Other links and lift over

dbSNP: rs5859; hg19: chr1-87328525;