Genetic Variant NM_006764.5:c.237G>C (chr3-50290414-C-G) – 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_006764.5(IFRD2):c.237G>C(p.Glu79Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00301 in 1,579,294 control chromosomes in the GnomAD database, including 161 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0041 ( 14 hom., cov: 33)

Exomes 𝑓: 0.0029 ( 147 hom. )

Consequence

IFRD2
NM_006764.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.121

Publications

2 publications found

Variant links:

Genes affected

IFRD2 (HGNC:5457): (interferon related developmental regulator 2) Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

IFRD2 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=0.004345238).

BP6

Variant 3-50290414-C-G is Benign according to our data. Variant chr3-50290414-C-G is described in ClinVar as [Benign]. Clinvar id is 771350.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.066 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFRD2	NM_006764.5 link	c.237G>C	p.Glu79Asp	missense_variant	Exon 3 of 12	ENST00000417626.8	NP_006755.5	Q12894

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFRD2	ENST00000417626.8 link	c.237G>C	p.Glu79Asp	missense_variant	Exon 3 of 12	1	NM_006764.5	ENSP00000402849.4		Q12894

Frequencies

GnomAD3 genomes

AF:

0.00406

AC:

618

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00109

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0284

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0208

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.00526

GnomAD2 exomes

AF:

0.0124

AC:

2405

AN:

194290

AF XY:

0.00969

show subpopulations

Gnomad AFR exome

AF:

0.000811

Gnomad AMR exome

AF:

0.0727

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0210

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000120

Gnomad OTH exome

AF:

0.00815

GnomAD4 exome

AF:

0.00289

AC:

4125

AN:

1426962

Hom.:

147

Cov.:

AF XY:

0.00260

AC XY:

1837

AN XY:

706628

show subpopulations

African (AFR)

AF:

0.000519

AC:

AN:

32746

American (AMR)

AF:

0.0681

AC:

2659

AN:

39026

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25480

East Asian (EAS)

AF:

0.0322

AC:

1221

AN:

37956

South Asian (SAS)

AF:

0.000256

AC:

AN:

81906

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51212

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5736

European-Non Finnish (NFE)

AF:

0.0000421

AC:

AN:

1093814

Other (OTH)

AF:

0.00272

AC:

161

AN:

59086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

264

529

793

1058

1322

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00412

AC:

627

AN:

152332

Hom.:

Cov.:

AF XY:

0.00428

AC XY:

319

AN XY:

74502

show subpopulations

African (AFR)

AF:

0.00108

AC:

AN:

41572

American (AMR)

AF:

0.0290

AC:

444

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.0208

AC:

108

AN:

5186

South Asian (SAS)

AF:

0.00145

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000191

AC:

AN:

68030

Other (OTH)

AF:

0.00473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

127

159

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00190

Hom.:

Bravo

AF:

0.00728

ESP6500AA

AF:

0.00120

AC:

ESP6500EA

AF:

0.000119

AC:

ExAC

AF:

0.00736

AC:

885

Asia WGS

AF:

0.0130

AC:

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Sep 11, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.51

CADD

Benign

8.6

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.026

T;T

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.61

LIST_S2

Benign

0.60

T;T

MetaRNN

Benign

0.0043

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

M;.

PhyloP100

-0.12

PrimateAI

Benign

0.45

PROVEAN

Benign

-1.6

.;N

REVEL

Benign

0.088

Sift

Benign

0.42

.;T

Sift4G

Benign

0.40

T;T

Polyphen

0.012

B;.

Vest4

0.23

ClinPred

0.0062

GERP RS

-2.9

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.6

Varity_R

0.079

gMVP

0.095

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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NM_006764.5:c.237G>C

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