dbSNP rs11674089: SELENOI:c.58-94G>A (chr2-26364208-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.69

Variant links:

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]

SELENOI links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
SELENOI	NM_033505.4 link	c.58-94G>A		intron_variant	Intron 1 of 9	ENST00000260585.12	NP_277040.1	Q9C0D9
SELENOI	NR_137633.2 link	n.148-94G>A		intron_variant	Intron 1 of 9

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SELENOI	ENST00000260585.12 link	c.58-94G>A	intron_variant	Intron 1 of 9	1	NM_033505.4	ENSP00000260585.7	Q9C0D9
SELENOI	ENST00000447170.1 link	c.58-94G>A	intron_variant	Intron 1 of 5	5		ENSP00000391804.1	C9JAG1
SELENOI	ENST00000442141.5 link	c.-39-94G>A	intron_variant	Intron 1 of 4	5		ENSP00000415280.1	C9JEZ2

Frequencies

GnomAD3 genomes

AF:

0.288

AC:

43462

AN:

151018

Hom.:

7186

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.290

AC XY:

21387

AN XY:

73790

show subpopulations

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

May 11, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over