1-86913954-C-T

Position:

• chr1-86913954-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.84+74G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0724 in 1,383,322 control chromosomes in the GnomAD database, including 5,285 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 0.12 (1628 hom., cov: 31)
  • Exomes 𝑓: 0.067 (3657 hom.)
• Consequence: SELENOF NM_004261.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.64

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SELENOF	NM_004261.5	c.84+74G>A		intron_variant		ENST00000331835.10	NP_004252.2
SELENOF	NM_203341.3	c.84+74G>A		intron_variant			NP_976086.1
SELENOF	NR_144512.1	n.161+361G>A		intron_variant
SELENOF	NR_144513.1	n.145+479G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SELENOF	ENST00000331835.10	c.84+74G>A		intron_variant		1	NM_004261.5	ENSP00000328729.6

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17491 AN: 151900 Hom.: 1623 Cov.: 31

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.0515

Gnomad AMR AF: 0.0684

Gnomad ASJ AF: 0.0990

Gnomad EAS AF: 0.00579

Gnomad SAS AF: 0.0432

Gnomad FIN AF: 0.0526

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0674

Gnomad OTH AF: 0.0977

GnomAD4 exome AF: 0.0671 AC: 82589 AN: 1231304 Hom.: 3657 Cov.: 17 AF XY: 0.0664 AC XY: 41366 AN XY: 622936

Gnomad4 AFR exome AF: 0.257

Gnomad4 AMR exome AF: 0.0422

Gnomad4 ASJ exome AF: 0.0915

Gnomad4 EAS exome AF: 0.0104

Gnomad4 SAS exome AF: 0.0521

Gnomad4 FIN exome AF: 0.0513

Gnomad4 NFE exome AF: 0.0657

Gnomad4 OTH exome AF: 0.0765

GnomAD4 genome AF: 0.115 AC: 17516 AN: 152018 Hom.: 1628 Cov.: 31 AF XY: 0.112 AC XY: 8306 AN XY: 74330

Gnomad4 AFR AF: 0.253

Gnomad4 AMR AF: 0.0682

Gnomad4 ASJ AF: 0.0990

Gnomad4 EAS AF: 0.00580

Gnomad4 SAS AF: 0.0433

Gnomad4 FIN AF: 0.0526

Gnomad4 NFE AF: 0.0674

Gnomad4 OTH AF: 0.0976

Alfa AF: 0.0579 Hom.: 87

Bravo AF: 0.119

Asia WGS AF: 0.0470 AC: 164 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.2
DANN	Benign	0.90

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: rs578851; hg19: chr1-87379637;