chr1-86862625-C-T

Position:

• chr1-86862625-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.*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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SELENOF	NM_004261.5	c.*849G>A		3_prime_UTR_variant	5/5	ENST00000331835.10	NP_004252.2
SELENOF	NM_203341.3	c.*922G>A		3_prime_UTR_variant	4/4		NP_976086.1
SELENOF	NR_144512.1	n.1424G>A		non_coding_transcript_exon_variant	5/5
SELENOF	NR_144513.1	n.1408G>A		non_coding_transcript_exon_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SELENOF	ENST00000331835.10	c.*849G>A		3_prime_UTR_variant	5/5	1	NM_004261.5	ENSP00000328729.6

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39311 AN: 151840 Hom.: 6268 Cov.: 33

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: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.259 AC: 39389 AN: 151958 Hom.: 6290 Cov.: 33 AF XY: 0.252 AC XY: 18741 AN XY: 74310

Gnomad4 AFR AF: 0.447

Gnomad4 AMR AF: 0.181

Gnomad4 ASJ AF: 0.179

Gnomad4 EAS AF: 0.0315

Gnomad4 SAS AF: 0.170

Gnomad4 FIN AF: 0.158

Gnomad4 NFE AF: 0.208

Gnomad4 OTH AF: 0.233

Alfa AF: 0.213 Hom.: 4563

Bravo AF: 0.265

Asia WGS AF: 0.164 AC: 567 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.10
DANN	Benign	0.29

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: rs540049; hg19: chr1-87328308;