dbSNP rs4787645: SEPHS2:c.-302G>A (chr16-30446029-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_012248.4(SEPHS2):c.-302G>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 313,606 control chromosomes in the GnomAD database, including 25,259 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 0.32 ( 10245 hom., cov: 31)

Exomes 𝑓: 0.40 ( 15014 hom. )

Consequence

SEPHS2
NM_012248.4 upstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0240

Publications

22 publications found

Variant links:

Genes affected

SEPHS2 (HGNC:19686): (selenophosphate synthetase 2) This gene encodes an enzyme that catalyzes the production of monoselenophosphate (MSP) from selenide and ATP. MSP is the selenium donor required for synthesis of selenocysteine (Sec), which is co-translationally incorporated into selenoproteins at in-frame UGA codons that normally signal translation termination. The 3' UTRs of selenoprotein mRNAs contain a conserved stem-loop structure, the Sec insertion sequence (SECIS) element, which is necessary for the recognition of UGA as a Sec codon rather than as a stop signal. This protein is itself a selenoprotein containing a Sec residue at its active site, suggesting the existence of an autoregulatory mechanism. It is preferentially expressed in tissues implicated in the synthesis of selenoproteins and in sites of blood cell development. A pseudogene for this locus has been identified on chromosome 5. [provided by RefSeq, May 2017]

SEPHS2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.847 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEPHS2	NM_012248.4 link	c.-302G>A		upstream_gene_variant		ENST00000478753.5	NP_036380.2	Q99611

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEPHS2	ENST00000478753.5 link	c.-302G>A		upstream_gene_variant		6	NM_012248.4	ENSP00000418669.3		Q99611

Frequencies

GnomAD3 genomes

AF:

0.316

AC:

47964

AN:

151652

Hom.:

10235

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0747

Gnomad AMI

AF:

0.237

Gnomad AMR

AF:

0.479

Gnomad ASJ

AF:

0.423

Gnomad EAS

AF:

0.868

Gnomad SAS

AF:

0.172

Gnomad FIN

AF:

0.491

Gnomad MID

AF:

0.329

Gnomad NFE

AF:

0.363

Gnomad OTH

AF:

0.343

GnomAD4 exome

AF:

0.398

AC:

64488

AN:

161836

Hom.:

15014

Cov.:

AF XY:

0.389

AC XY:

32438

AN XY:

83408

show subpopulations

African (AFR)

AF:

0.0806

AC:

354

AN:

4390

American (AMR)

AF:

0.535

AC:

2669

AN:

4988

Ashkenazi Jewish (ASJ)

AF:

0.395

AC:

2317

AN:

5866

East Asian (EAS)

AF:

0.868

AC:

10192

AN:

11744

South Asian (SAS)

AF:

0.170

AC:

1751

AN:

10312

European-Finnish (FIN)

AF:

0.494

AC:

6495

AN:

13156

Middle Eastern (MID)

AF:

0.352

AC:

287

AN:

816

European-Non Finnish (NFE)

AF:

0.364

AC:

36497

AN:

100170

Other (OTH)

AF:

0.378

AC:

3926

AN:

10394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1720

3440

5159

6879

8599

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

222

444

666

888

1110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.316

AC:

47976

AN:

151770

Hom.:

10245

Cov.:

AF XY:

0.324

AC XY:

24026

AN XY:

74158

show subpopulations

African (AFR)

AF:

0.0746

AC:

3091

AN:

41428

American (AMR)

AF:

0.480

AC:

7296

AN:

15198

Ashkenazi Jewish (ASJ)

AF:

0.423

AC:

1470

AN:

3472

East Asian (EAS)

AF:

0.868

AC:

4459

AN:

5136

South Asian (SAS)

AF:

0.172

AC:

828

AN:

4808

European-Finnish (FIN)

AF:

0.491

AC:

5161

AN:

10518

Middle Eastern (MID)

AF:

0.316

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.363

AC:

24643

AN:

67908

Other (OTH)

AF:

0.343

AC:

720

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1433

2866

4299

5732

7165

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

450

900

1350

1800

2250

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.342

Hom.:

14177

Bravo

AF:

0.317

Asia WGS

AF:

0.453

AC:

1573

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

4.7

(source)

DANN

Benign

0.71

PhyloP100

-0.024

PromoterAI

-0.17

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over