rs5845

Variant names:

• chr1-86863156-G-A
• rs5845
• NM_004261.5:c.*318C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004261.5(SELENOF):​c.*318C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 216,292 control chromosomes in the GnomAD database, including 10,924 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 (9388 hom., cov: 32)
  • Exomes 𝑓: 0.20 (1536 hom.)
• Consequence: SELENOF NM_004261.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.01
• Publications: 42 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=-0.5).
• 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.*318C>T		3_prime_UTR_variant	Exon 5 of 5	ENST00000331835.10	NP_004252.2
SELENOF	NR_144512.1	n.893C>T		non_coding_transcript_exon_variant	Exon 5 of 5
SELENOF	NR_144513.1	n.877C>T		non_coding_transcript_exon_variant	Exon 5 of 5
SELENOF	NM_203341.3	c.*391C>T		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.*318C>T		3_prime_UTR_variant	Exon 5 of 5	1	NM_004261.5	ENSP00000328729.6

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46404 AN: 151936 Hom.: 9363 Cov.: 32

Gnomad AFR AF: 0.577

Gnomad AMI AF: 0.180

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.0308

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.266

GnomAD4 exome AF: 0.199 AC: 12790 AN: 64236 Hom.: 1536 Cov.: 0 AF XY: 0.196 AC XY: 6551 AN XY: 33420

African (AFR) AF: 0.560 AC: 807 AN: 1442

American (AMR) AF: 0.165 AC: 376 AN: 2276

Ashkenazi Jewish (ASJ) AF: 0.156 AC: 301 AN: 1934

East Asian (EAS) AF: 0.0347 AC: 95 AN: 2738

South Asian (SAS) AF: 0.168 AC: 1133 AN: 6762

European-Finnish (FIN) AF: 0.210 AC: 819 AN: 3908

Middle Eastern (MID) AF: 0.195 AC: 55 AN: 282

European-Non Finnish (NFE) AF: 0.203 AC: 8330 AN: 40964

Other (OTH) AF: 0.222 AC: 874 AN: 3930

GnomAD4 genome AF: 0.306 AC: 46495 AN: 152056 Hom.: 9388 Cov.: 32 AF XY: 0.299 AC XY: 22196 AN XY: 74332

African (AFR) AF: 0.577 AC: 23922 AN: 41452

American (AMR) AF: 0.197 AC: 3004 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 630 AN: 3470

East Asian (EAS) AF: 0.0311 AC: 161 AN: 5180

South Asian (SAS) AF: 0.183 AC: 881 AN: 4822

European-Finnish (FIN) AF: 0.207 AC: 2184 AN: 10562

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

European-Non Finnish (NFE) AF: 0.219 AC: 14919 AN: 67974

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

Alfa AF: 0.266 Hom.: 9314

Bravo AF: 0.313

Asia WGS AF: 0.181 AC: 631 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	13
DANN	Benign	0.86
PhyloP100		2.0
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: rs5845; hg19: chr1-87328839;