chr1-86912944-T-C

Variant names:

• chr1-86912944-T-C
• rs1407131
• NM_004261.5:c.84+1084A>G

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+1084A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 152,116 control chromosomes in the GnomAD database, including 1,228 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 (1228 hom., cov: 32)
• Consequence: SELENOF NM_004261.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.401
• Publications: 13 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.136 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SELENOF	NM_004261.5	MANE Select	c.84+1084A>G		intron	N/A	NP_004252.2
	SELENOF	NM_203341.3		c.84+1084A>G		intron	N/A	NP_976086.1	O60613-2
	SELENOF	NR_144512.1		n.161+1371A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SELENOF	ENST00000331835.10	TSL:1 MANE Select	c.84+1084A>G		intron	N/A	ENSP00000328729.6	O60613-1
	SELENOF	ENST00000370554.5	TSL:1	c.84+1084A>G		intron	N/A	ENSP00000359585.2	O60613-2
	SELENOF	ENST00000401030.4	TSL:2	c.84+1084A>G		intron	N/A	ENSP00000383810.4	A8MZD0

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18638 AN: 151998 Hom.: 1222 Cov.: 32

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.0955

Gnomad ASJ AF: 0.0748

Gnomad EAS AF: 0.0254

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.111

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

GnomAD4 genome AF: 0.123 AC: 18679 AN: 152116 Hom.: 1228 Cov.: 32 AF XY: 0.120 AC XY: 8889 AN XY: 74380

African (AFR) AF: 0.128 AC: 5323 AN: 41468

American (AMR) AF: 0.0959 AC: 1466 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0748 AC: 259 AN: 3464

East Asian (EAS) AF: 0.0257 AC: 133 AN: 5182

South Asian (SAS) AF: 0.125 AC: 602 AN: 4824

European-Finnish (FIN) AF: 0.105 AC: 1116 AN: 10590

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.138 AC: 9405 AN: 67990

Other (OTH) AF: 0.112 AC: 236 AN: 2110

Alfa AF: 0.132 Hom.: 3764

Bravo AF: 0.123

Asia WGS AF: 0.110 AC: 384 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.8
DANN	Benign	0.76
PhyloP100		-0.40
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: rs1407131; hg19: chr1-87378627;