rs2783974

Positions:

• chr1-86869277-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.317-1175G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0823 in 152,200 control chromosomes in the GnomAD database, including 683 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 0.082 (683 hom., cov: 32)
• Consequence: SELENOF NM_004261.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.331

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 (NFE) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SELENOF	NM_004261.5	c.317-1175G>A		intron_variant		ENST00000331835.10
SELENOF	NM_203341.3	c.317-5672G>A		intron_variant
SELENOF	NR_144512.1	n.394-1175G>A		intron_variant, non_coding_transcript_variant
SELENOF	NR_144513.1	n.378-1175G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SELENOF	ENST00000331835.10	c.317-1175G>A		intron_variant		1	NM_004261.5	P1

Frequencies

GnomAD3 genomes AF: 0.0822 AC: 12504 AN: 152082 Hom.: 682 Cov.: 32

Gnomad AFR AF: 0.0264

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.0749

Gnomad ASJ AF: 0.0617

Gnomad EAS AF: 0.0216

Gnomad SAS AF: 0.0725

Gnomad FIN AF: 0.0934

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.0757

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

GnomAD4 genome AF: 0.0823 AC: 12519 AN: 152200 Hom.: 683 Cov.: 32 AF XY: 0.0800 AC XY: 5955 AN XY: 74400

Gnomad4 AFR AF: 0.0264

Gnomad4 AMR AF: 0.0753

Gnomad4 ASJ AF: 0.0617

Gnomad4 EAS AF: 0.0218

Gnomad4 SAS AF: 0.0723

Gnomad4 FIN AF: 0.0934

Gnomad4 NFE AF: 0.123

Gnomad4 OTH AF: 0.0754

Alfa AF: 0.112 Hom.: 147

Bravo AF: 0.0783

Asia WGS AF: 0.0640 AC: 224 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.7
DANN	Benign	0.69

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: rs2783974; hg19: chr1-87334960;