1-86913954-C-T

Variant names:

• chr1-86913954-C-T
• rs578851
• NM_004261.5:c.84+74G>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.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
• Publications: 5 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.249 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.84+74G>A		intron	N/A	NP_004252.2
	SELENOF	NM_203341.3		c.84+74G>A		intron	N/A	NP_976086.1
	SELENOF	NR_144512.1		n.161+361G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SELENOF	ENST00000331835.10	TSL:1 MANE Select	c.84+74G>A		intron	N/A	ENSP00000328729.6
	SELENOF	ENST00000370554.5	TSL:1	c.84+74G>A		intron	N/A	ENSP00000359585.2
	SELENOF	ENST00000467557.1	TSL:5	n.*17G>A		non_coding_transcript_exon	Exon 1 of 4	ENSP00000488471.1

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

African (AFR) AF: 0.257 AC: 7414 AN: 28876

American (AMR) AF: 0.0422 AC: 1860 AN: 44054

Ashkenazi Jewish (ASJ) AF: 0.0915 AC: 2259 AN: 24702

East Asian (EAS) AF: 0.0104 AC: 401 AN: 38604

South Asian (SAS) AF: 0.0521 AC: 4256 AN: 81766

European-Finnish (FIN) AF: 0.0513 AC: 2732 AN: 53216

Middle Eastern (MID) AF: 0.0612 AC: 326 AN: 5330

European-Non Finnish (NFE) AF: 0.0657 AC: 59294 AN: 901858

Other (OTH) AF: 0.0765 AC: 4047 AN: 52898

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

African (AFR) AF: 0.253 AC: 10473 AN: 41400

American (AMR) AF: 0.0682 AC: 1042 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0990 AC: 343 AN: 3466

East Asian (EAS) AF: 0.00580 AC: 30 AN: 5170

South Asian (SAS) AF: 0.0433 AC: 208 AN: 4806

European-Finnish (FIN) AF: 0.0526 AC: 557 AN: 10588

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0674 AC: 4580 AN: 68002

Other (OTH) AF: 0.0976 AC: 206 AN: 2110

Alfa AF: 0.0652 Hom.: 162

Bravo AF: 0.119

Asia WGS AF: 0.0470 AC: 164 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.2
DANN	Benign	0.90
PhyloP100		-1.6
PromoterAI		-0.11	Neutral
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: rs578851; hg19: chr1-87379637;