chr1-86891007-T-C

Variant names:

• chr1-86891007-T-C
• rs486133
• NM_004261.5:c.253-10282A>G

Variant summary

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

The NM_004261.5(SELENOF):​c.253-10282A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 151,766 control chromosomes in the GnomAD database, including 5,061 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 0.24 (5061 hom., cov: 31)
• Consequence: SELENOF NM_004261.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00600

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SELENOF	NM_004261.5	c.253-10282A>G		intron_variant	Intron 2 of 4	ENST00000331835.10	NP_004252.2
SELENOF	NM_203341.3	c.253-10282A>G		intron_variant	Intron 2 of 3		NP_976086.1
SELENOF	NR_144512.1	n.330-10282A>G		intron_variant	Intron 2 of 4
SELENOF	NR_144513.1	n.314-10282A>G		intron_variant	Intron 2 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SELENOF	ENST00000331835.10	c.253-10282A>G		intron_variant	Intron 2 of 4	1	NM_004261.5	ENSP00000328729.6

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36130 AN: 151648 Hom.: 5045 Cov.: 31

Gnomad AFR AF: 0.383

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.164

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.0312

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.211

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.239 AC: 36198 AN: 151766 Hom.: 5061 Cov.: 31 AF XY: 0.232 AC XY: 17208 AN XY: 74176

Gnomad4 AFR AF: 0.383

Gnomad4 AMR AF: 0.164

Gnomad4 ASJ AF: 0.174

Gnomad4 EAS AF: 0.0315

Gnomad4 SAS AF: 0.170

Gnomad4 FIN AF: 0.155

Gnomad4 NFE AF: 0.206

Gnomad4 OTH AF: 0.212

Alfa AF: 0.230 Hom.: 902

Bravo AF: 0.242

Asia WGS AF: 0.158 AC: 550 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.9
DANN	Benign	0.47

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: rs486133; hg19: chr1-87356690;