rs5859

Variant names:

• chr1-86862842-C-T
• rs5859
• NM_004261.5:c.*632G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 44 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=-0.76).
• 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 rank	MANE	Protein	UniProt
SELENOF	NM_004261.5	c.*632G>A		3_prime_UTR_variant	Exon 5 of 5	ENST00000331835.10	NP_004252.2
SELENOF	NR_144512.1	n.1207G>A		non_coding_transcript_exon_variant	Exon 5 of 5
SELENOF	NR_144513.1	n.1191G>A		non_coding_transcript_exon_variant	Exon 5 of 5
SELENOF	NM_203341.3	c.*705G>A		3_prime_UTR_variant	Exon 4 of 4		NP_976086.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SELENOF	ENST00000331835.10	c.*632G>A		3_prime_UTR_variant	Exon 5 of 5	1	NM_004261.5	ENSP00000328729.6
SELENOF	ENST00000370554.5	c.*705G>A		3_prime_UTR_variant	Exon 4 of 4	1		ENSP00000359585.2
SELENOF	ENST00000648872.1	n.*847G>A		non_coding_transcript_exon_variant	Exon 6 of 6			ENSP00000497584.1
SELENOF	ENST00000648872.1	n.*847G>A		3_prime_UTR_variant	Exon 6 of 6			ENSP00000497584.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.212 AC: 70 AN: 330

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AF: 1.00 AC: 4 AN: 4

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

African (AFR) AF: 0.577 AC: 23911 AN: 41444

American (AMR) AF: 0.197 AC: 3004 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 630 AN: 3464

East Asian (EAS) AF: 0.0314 AC: 163 AN: 5188

South Asian (SAS) AF: 0.183 AC: 885 AN: 4828

European-Finnish (FIN) AF: 0.208 AC: 2196 AN: 10564

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.219 AC: 14915 AN: 67966

Other (OTH) AF: 0.268 AC: 565 AN: 2112

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
PhyloP100		0.63
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: rs5859; hg19: chr1-87328525;