Genetic Variant NM_058164.4:c.317G>A (chr19-9857758-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_058164.4(OLFM2):c.317G>A(p.Arg106Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.506 in 1,613,768 control chromosomes in the GnomAD database, including 217,891 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.41 ( 15418 hom., cov: 32)

Exomes 𝑓: 0.52 ( 202473 hom. )

Consequence

OLFM2
NM_058164.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.625

Publications

29 publications found

Variant links:

Genes affected

OLFM2 (HGNC:17189): (olfactomedin 2) Involved in positive regulation of smooth muscle cell differentiation. Acts upstream of or within protein secretion. Located in cytoplasm; extracellular region; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

OLFM2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=8.5246563E-4).

BP6

Variant 19-9857758-C-T is Benign according to our data. Variant chr19-9857758-C-T is described in ClinVar as Benign. ClinVar VariationId is 1297260.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.54 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OLFM2	NM_058164.4 link	c.317G>A	p.Arg106Gln	missense_variant	Exon 3 of 6	ENST00000264833.9	NP_477512.1	O95897
OLFM2	NM_001304347.2 link	c.389G>A	p.Arg130Gln	missense_variant	Exon 3 of 6		NP_001291276.1	O95897K7EKW2
OLFM2	NM_001304348.2 link	c.83G>A	p.Arg28Gln	missense_variant	Exon 2 of 5		NP_001291277.1	O95897K7EIS8
OLFM2	XM_047439713.1 link	c.113G>A	p.Arg38Gln	missense_variant	Exon 3 of 6		XP_047295669.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OLFM2	ENST00000264833.9 link	c.317G>A	p.Arg106Gln	missense_variant	Exon 3 of 6	1	NM_058164.4	ENSP00000264833.3		O95897

Frequencies

GnomAD3 genomes

AF:

0.407

AC:

61784

AN:

151888

Hom.:

15422

Cov.:

show subpopulations

Gnomad AFR

AF:

0.114

Gnomad AMI

AF:

0.325

Gnomad AMR

AF:

0.546

Gnomad ASJ

AF:

0.532

Gnomad EAS

AF:

0.296

Gnomad SAS

AF:

0.304

Gnomad FIN

AF:

0.532

Gnomad MID

AF:

0.417

Gnomad NFE

AF:

0.544

Gnomad OTH

AF:

0.424

GnomAD2 exomes

AF:

0.475

AC:

119182

AN:

251110

AF XY:

0.469

show subpopulations

Gnomad AFR exome

AF:

0.106

Gnomad AMR exome

AF:

0.610

Gnomad ASJ exome

AF:

0.525

Gnomad EAS exome

AF:

0.297

Gnomad FIN exome

AF:

0.554

Gnomad NFE exome

AF:

0.540

Gnomad OTH exome

AF:

0.509

GnomAD4 exome

AF:

0.516

AC:

754682

AN:

1461764

Hom.:

202473

Cov.:

AF XY:

0.510

AC XY:

370806

AN XY:

727174

show subpopulations

African (AFR)

AF:

0.0964

AC:

3228

AN:

33476

American (AMR)

AF:

0.600

AC:

26846

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.520

AC:

13582

AN:

26136

East Asian (EAS)

AF:

0.300

AC:

11900

AN:

39700

South Asian (SAS)

AF:

0.302

AC:

26036

AN:

86256

European-Finnish (FIN)

AF:

0.560

AC:

29909

AN:

53412

Middle Eastern (MID)

AF:

0.418

AC:

2395

AN:

5724

European-Non Finnish (NFE)

AF:

0.550

AC:

611792

AN:

1111956

Other (OTH)

AF:

0.480

AC:

28994

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

22330

44660

66991

89321

111651

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16956

33912

50868

67824

84780

<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:

0.406

AC:

61779

AN:

152004

Hom.:

15418

Cov.:

AF XY:

0.406

AC XY:

30132

AN XY:

74288

show subpopulations

African (AFR)

AF:

0.114

AC:

4711

AN:

41472

American (AMR)

AF:

0.546

AC:

8325

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.532

AC:

1848

AN:

3472

East Asian (EAS)

AF:

0.296

AC:

1529

AN:

5174

South Asian (SAS)

AF:

0.305

AC:

1470

AN:

4818

European-Finnish (FIN)

AF:

0.532

AC:

5626

AN:

10570

Middle Eastern (MID)

AF:

0.410

AC:

119

AN:

290

European-Non Finnish (NFE)

AF:

0.544

AC:

36968

AN:

67936

Other (OTH)

AF:

0.421

AC:

887

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1625

3250

4876

6501

8126

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

566

1132

1698

2264

2830

<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:

0.488

Hom.:

59565

Bravo

AF:

0.397

TwinsUK

AF:

0.551

AC:

2044

ALSPAC

AF:

0.553

AC:

2130

ESP6500AA

AF:

0.128

AC:

564

ESP6500EA

AF:

0.549

AC:

4718

ExAC

AF:

0.458

AC:

55603

Asia WGS

AF:

0.304

AC:

1056

AN:

3478

EpiCase

AF:

0.536

EpiControl

AF:

0.534

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 17122126) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.57

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

T;.;T

Eigen

Benign

0.017

Eigen_PC

Benign

0.031

FATHMM_MKL

Benign

0.28

LIST_S2

Uncertain

0.93

D;D;D

MetaRNN

Benign

0.00085

T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.69

N;.;.

PhyloP100

0.63

PrimateAI

Uncertain

0.58

PROVEAN

Benign

0.12

N;.;.

REVEL

Benign

0.095

Sift

Uncertain

0.015

D;.;.

Sift4G

Benign

0.075

T;T;.

Polyphen

0.94

P;.;.

Vest4

0.050

MPC

0.83

ClinPred

0.018

GERP RS

3.9

PromoterAI

0.031

Neutral

(source)

Varity_R

0.090

Mutation Taster

=99/1

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over