chr1-86891007-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SELENOF	NM_004261.5	MANE Select	c.253-10282A>G		intron	N/A	NP_004252.2
	SELENOF	NM_203341.3		c.253-10282A>G		intron	N/A	NP_976086.1
	SELENOF	NR_144512.1		n.330-10282A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SELENOF	ENST00000331835.10	TSL:1 MANE Select	c.253-10282A>G		intron	N/A	ENSP00000328729.6
	SELENOF	ENST00000370554.5	TSL:1	c.253-10282A>G		intron	N/A	ENSP00000359585.2
	SELENOF	ENST00000401030.4	TSL:2	c.253-3811A>G		intron	N/A	ENSP00000383810.4

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

African (AFR) AF: 0.383 AC: 15854 AN: 41382

American (AMR) AF: 0.164 AC: 2503 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 603 AN: 3470

East Asian (EAS) AF: 0.0315 AC: 163 AN: 5176

South Asian (SAS) AF: 0.170 AC: 819 AN: 4820

European-Finnish (FIN) AF: 0.155 AC: 1621 AN: 10428

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.206 AC: 13971 AN: 67930

Other (OTH) AF: 0.212 AC: 448 AN: 2110

Alfa AF: 0.235 Hom.: 974

Bravo AF: 0.242

Asia WGS AF: 0.158 AC: 550 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.9
DANN	Benign	0.47
PhyloP100		0.0060
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs486133; hg19: chr1-87356690;