dbSNP rs10494394: SESN2:c.*1025A>G (chr1-28281827-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_031459.5(SESN2):c.*1025A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0293 in 152,258 control chromosomes in the GnomAD database, including 102 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 0.029 ( 102 hom., cov: 32)

Exomes 𝑓: 0.013 ( 0 hom. )

Consequence

SESN2
NM_031459.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.231

Publications

6 publications found

Variant links:

Genes affected

SESN2 (HGNC:20746): (sestrin 2) This gene encodes a member of the sestrin family of PA26-related proteins. The encoded protein may function in the regulation of cell growth and survival. This protein may be involved in cellular response to different stress conditions. [provided by RefSeq, Jul 2008]

SESN2 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=-0.52).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0293 (4454/152178) while in subpopulation NFE AF = 0.05 (3401/67976). AF 95% confidence interval is 0.0486. There are 102 homozygotes in GnomAd4. There are 1936 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 102 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031459.5. 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
	SESN2	NM_031459.5	MANE Select	c.*1025A>G		3_prime_UTR	Exon 10 of 10	NP_113647.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SESN2	ENST00000253063.4	TSL:1 MANE Select	c.*1025A>G		3_prime_UTR	Exon 10 of 10	ENSP00000253063.3

Frequencies

GnomAD3 genomes

AF:

0.0293

AC:

4457

AN:

152060

Hom.:

102

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00864

Gnomad AMI

AF:

0.0318

Gnomad AMR

AF:

0.0191

Gnomad ASJ

AF:

0.0153

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00664

Gnomad FIN

AF:

0.0218

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0500

Gnomad OTH

AF:

0.0273

GnomAD4 exome

AF:

0.0125

AC:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0152

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0293

AC:

4454

AN:

152178

Hom.:

102

Cov.:

AF XY:

0.0260

AC XY:

1936

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.00862

AC:

358

AN:

41538

American (AMR)

AF:

0.0190

AC:

291

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.0153

AC:

AN:

3470

East Asian (EAS)

AF:

0.000387

AC:

AN:

5164

South Asian (SAS)

AF:

0.00644

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.0218

AC:

231

AN:

10612

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0500

AC:

3401

AN:

67976

Other (OTH)

AF:

0.0270

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

227

454

682

909

1136

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

162

216

270

<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:

0.0418

Hom.:

252

Bravo

AF:

0.0282

Asia WGS

AF:

0.00375

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

7.4

(source)

DANN

Benign

0.89

PhyloP100

0.23

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over