rs11674089

chr2-26364208-G-Achr2-26364208-G-Cchr2-26364208-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_033505.4(SELENOI):c.58-94G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 908,394 control chromosomes in the GnomAD database, including 50,588 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.29 (7190 hom., cov: 30)
  • Exomes 𝑓: 0.33 (43398 hom.)
• Consequence: SELENOI NM_033505.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.69

Genes affected

SELENOI (HGNC:29361): (selenoprotein I) The multi-pass transmembrane protein encoded by this gene belongs to the CDP-alcohol phosphatidyltransferase class-I family. It catalyzes the transfer of phosphoethanolamine from CDP-ethanolamine to diacylglycerol to produce phosphatidylethanolamine, which is involved in the formation and maintenance of vesicular membranes, regulation of lipid metabolism, and protein folding. This protein is a selenoprotein, containing the rare selenocysteine (Sec) amino acid at its active site. 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, Jul 2016]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.06).
• BP6: Variant 2-26364208-G-A is Benign according to our data. Variant chr2-26364208-G-A is described in ClinVar as [Benign]. Clinvar id is 1239310.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SELENOI	NM_033505.4	c.58-94G>A		intron_variant		ENST00000260585.12
SELENOI	NR_137633.2	n.148-94G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SELENOI	ENST00000260585.12	c.58-94G>A		intron_variant		1	NM_033505.4	P1
SELENOI	ENST00000442141.5	c.-39-94G>A		intron_variant		5
SELENOI	ENST00000447170.1	c.58-94G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43462 AN: 151018 Hom.: 7186 Cov.: 30

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.323

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.448

Gnomad EAS AF: 0.256

Gnomad SAS AF: 0.304

Gnomad FIN AF: 0.420

Gnomad MID AF: 0.384

Gnomad NFE AF: 0.358

Gnomad OTH AF: 0.324

GnomAD4 exome AF: 0.334 AC: 252550 AN: 757262 Hom.: 43398 AF XY: 0.333 AC XY: 132228 AN XY: 396772

Gnomad4 AFR exome AF: 0.104

Gnomad4 AMR exome AF: 0.315

Gnomad4 ASJ exome AF: 0.457

Gnomad4 EAS exome AF: 0.196

Gnomad4 SAS exome AF: 0.299

Gnomad4 FIN exome AF: 0.414

Gnomad4 NFE exome AF: 0.344

Gnomad4 OTH exome AF: 0.337

GnomAD4 genome AF: 0.288 AC: 43462 AN: 151132 Hom.: 7190 Cov.: 30 AF XY: 0.290 AC XY: 21387 AN XY: 73790

Gnomad4 AFR AF: 0.115

Gnomad4 AMR AF: 0.309

Gnomad4 ASJ AF: 0.448

Gnomad4 EAS AF: 0.256

Gnomad4 SAS AF: 0.304

Gnomad4 FIN AF: 0.420

Gnomad4 NFE AF: 0.358

Gnomad4 OTH AF: 0.325

Alfa AF: 0.338 Hom.: 4263

Bravo AF: 0.273

Asia WGS AF: 0.301 AC: 1048 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 11, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
Cadd	Benign	0.096
Dann	Benign	0.62

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: rs11674089; hg19: chr2-26587076; COSMIC: COSV53143379;