Genetic Variant NM_016470.8:c.221T>G (chr20-44197710-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_016470.8(OSER1):c.221T>G(p.Val74Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 1,608,734 control chromosomes in the GnomAD database, including 34,241 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.26 ( 7546 hom., cov: 32)

Exomes 𝑓: 0.17 ( 26695 hom. )

Consequence

OSER1
NM_016470.8 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.961

Publications

31 publications found

Variant links:

Genes affected

OSER1 (HGNC:16105): (oxidative stress responsive serine rich 1) Predicted to be involved in cellular response to hydrogen peroxide. [provided by Alliance of Genome Resources, Apr 2022]

OSER1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=3.0824542E-4).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.512 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OSER1	NM_016470.8 link	c.221T>G	p.Val74Gly	missense_variant	Exon 4 of 4	ENST00000255174.3	NP_057554.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OSER1	ENST00000255174.3 link	c.221T>G	p.Val74Gly	missense_variant	Exon 4 of 4	1	NM_016470.8	ENSP00000255174.2
OSER1	ENST00000372970.6 link	c.221T>G	p.Val74Gly	missense_variant	Exon 6 of 6	3		ENSP00000362061.1

Frequencies

GnomAD3 genomes

AF:

0.265

AC:

40241

AN:

151980

Hom.:

7528

Cov.:

show subpopulations

Gnomad AFR

AF:

0.517

Gnomad AMI

AF:

0.112

Gnomad AMR

AF:

0.152

Gnomad ASJ

AF:

0.181

Gnomad EAS

AF:

0.422

Gnomad SAS

AF:

0.337

Gnomad FIN

AF:

0.177

Gnomad MID

AF:

0.201

Gnomad NFE

AF:

0.141

Gnomad OTH

AF:

0.219

GnomAD2 exomes

AF:

0.215

AC:

53983

AN:

251188

AF XY:

0.216

show subpopulations

Gnomad AFR exome

AF:

0.526

Gnomad AMR exome

AF:

0.128

Gnomad ASJ exome

AF:

0.172

Gnomad EAS exome

AF:

0.430

Gnomad FIN exome

AF:

0.185

Gnomad NFE exome

AF:

0.141

Gnomad OTH exome

AF:

0.181

GnomAD4 exome

AF:

0.168

AC:

244680

AN:

1456634

Hom.:

26695

Cov.:

AF XY:

0.172

AC XY:

124933

AN XY:

724884

show subpopulations

African (AFR)

AF:

0.528

AC:

17588

AN:

33294

American (AMR)

AF:

0.130

AC:

5817

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.172

AC:

4483

AN:

26088

East Asian (EAS)

AF:

0.429

AC:

17013

AN:

39652

South Asian (SAS)

AF:

0.331

AC:

28491

AN:

86068

European-Finnish (FIN)

AF:

0.193

AC:

10329

AN:

53388

Middle Eastern (MID)

AF:

0.200

AC:

1149

AN:

5744

European-Non Finnish (NFE)

AF:

0.134

AC:

148050

AN:

1107532

Other (OTH)

AF:

0.195

AC:

11760

AN:

60160

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.447

Heterozygous variant carriers

8462

16924

25385

33847

42309

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5682

11364

17046

22728

28410

<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:

0.265

AC:

40299

AN:

152100

Hom.:

7546

Cov.:

AF XY:

0.267

AC XY:

19879

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.518

AC:

21441

AN:

41428

American (AMR)

AF:

0.152

AC:

2318

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.181

AC:

628

AN:

3472

East Asian (EAS)

AF:

0.422

AC:

2183

AN:

5178

South Asian (SAS)

AF:

0.335

AC:

1615

AN:

4818

European-Finnish (FIN)

AF:

0.177

AC:

1871

AN:

10600

Middle Eastern (MID)

AF:

0.207

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.141

AC:

9617

AN:

68002

Other (OTH)

AF:

0.219

AC:

463

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1312

2623

3935

5246

6558

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

394

788

1182

1576

1970

<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:

0.180

Hom.:

13077

Bravo

AF:

0.273

TwinsUK

AF:

0.136

AC:

505

ALSPAC

AF:

0.142

AC:

549

ESP6500AA

AF:

0.507

AC:

2235

ESP6500EA

AF:

0.141

AC:

1215

ExAC

AF:

0.224

AC:

27148

Asia WGS

AF:

0.352

AC:

1225

AN:

3478

EpiCase

AF:

0.145

EpiControl

AF:

0.146

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.048

T;T

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.28

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.61

.;T

MetaRNN

Benign

0.00031

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

2.0

M;M

PhyloP100

0.96

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.9

N;N

REVEL

Benign

0.036

Sift

Uncertain

0.018

D;D

Sift4G

Benign

0.17

T;T

Polyphen

0.062

B;B

Vest4

0.14

MPC

0.44

ClinPred

0.0074

GERP RS

1.0

Varity_R

0.11

gMVP

0.19

Mutation Taster

=96/4

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