Genetic Variant NM_032023.4:c.262A>G (chr10-44982644-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_032023.4(RASSF4):c.262A>G(p.Arg88Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 1,612,882 control chromosomes in the GnomAD database, including 31,566 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 0.23 ( 4361 hom., cov: 33)

Exomes 𝑓: 0.19 ( 27205 hom. )

Consequence

RASSF4
NM_032023.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.01

Publications

34 publications found

Variant links:

Genes affected

RASSF4 (HGNC:20793): (Ras association domain family member 4) The function of this gene has not yet been determined but may involve a role in tumor suppression. Alternative splicing of this gene results in several transcript variants; however, most of the variants have not been fully described. [provided by RefSeq, Jul 2008]

RASSF4 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 (MetaRNN=0.0047510862).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.333 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RASSF4	NM_032023.4 link	c.262A>G	p.Arg88Gly	missense_variant	Exon 4 of 11	ENST00000340258.10	NP_114412.2	Q9H2L5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RASSF4	ENST00000340258.10 link	c.262A>G	p.Arg88Gly	missense_variant	Exon 4 of 11	1	NM_032023.4	ENSP00000339692.4		Q9H2L5-1

Frequencies

GnomAD3 genomes

AF:

0.227

AC:

34531

AN:

152018

Hom.:

4349

Cov.:

show subpopulations

Gnomad AFR

AF:

0.338

Gnomad AMI

AF:

0.163

Gnomad AMR

AF:

0.159

Gnomad ASJ

AF:

0.161

Gnomad EAS

AF:

0.312

Gnomad SAS

AF:

0.291

Gnomad FIN

AF:

0.163

Gnomad MID

AF:

0.269

Gnomad NFE

AF:

0.179

Gnomad OTH

AF:

0.204

GnomAD2 exomes

AF:

0.198

AC:

49452

AN:

249644

AF XY:

0.202

show subpopulations

Gnomad AFR exome

AF:

0.344

Gnomad AMR exome

AF:

0.0995

Gnomad ASJ exome

AF:

0.159

Gnomad EAS exome

AF:

0.317

Gnomad FIN exome

AF:

0.164

Gnomad NFE exome

AF:

0.174

Gnomad OTH exome

AF:

0.191

GnomAD4 exome

AF:

0.187

AC:

272848

AN:

1460746

Hom.:

27205

Cov.:

AF XY:

0.189

AC XY:

137685

AN XY:

726654

show subpopulations

African (AFR)

AF:

0.344

AC:

11508

AN:

33430

American (AMR)

AF:

0.104

AC:

4643

AN:

44596

Ashkenazi Jewish (ASJ)

AF:

0.158

AC:

4130

AN:

26058

East Asian (EAS)

AF:

0.316

AC:

12526

AN:

39668

South Asian (SAS)

AF:

0.283

AC:

24372

AN:

86156

European-Finnish (FIN)

AF:

0.166

AC:

8846

AN:

53396

Middle Eastern (MID)

AF:

0.228

AC:

1304

AN:

5722

European-Non Finnish (NFE)

AF:

0.174

AC:

193751

AN:

1111390

Other (OTH)

AF:

0.195

AC:

11768

AN:

60330

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

11982

23963

35945

47926

59908

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.227

AC:

34564

AN:

152136

Hom.:

4361

Cov.:

AF XY:

0.226

AC XY:

16825

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.338

AC:

14029

AN:

41498

American (AMR)

AF:

0.159

AC:

2434

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.161

AC:

559

AN:

3468

East Asian (EAS)

AF:

0.311

AC:

1607

AN:

5168

South Asian (SAS)

AF:

0.290

AC:

1399

AN:

4832

European-Finnish (FIN)

AF:

0.163

AC:

1730

AN:

10602

Middle Eastern (MID)

AF:

0.279

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.179

AC:

12148

AN:

67952

Other (OTH)

AF:

0.202

AC:

427

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1400

2800

4200

5600

7000

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.193

Hom.:

11295

Bravo

AF:

0.228

TwinsUK

AF:

0.174

AC:

645

ALSPAC

AF:

0.180

AC:

694

ESP6500AA

AF:

0.337

AC:

1484

ESP6500EA

AF:

0.174

AC:

1499

ExAC

AF:

0.204

AC:

24751

Asia WGS

AF:

0.279

AC:

968

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.048

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Benign

0.44

DEOGEN2

Benign

0.00029

T;T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0083

LIST_S2

Benign

0.11

T;T;T

MetaRNN

Benign

0.0048

T;T;T

MetaSVM

Benign

-0.91

PhyloP100

2.0

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.20

N;N;N

REVEL

Benign

0.11

Sift

Benign

0.41

T;T;T

Sift4G

Benign

0.39

T;T;T

Polyphen

0.0

B;.;.

Vest4

0.023

MPC

0.13

ClinPred

0.0017

GERP RS

1.4

Varity_R

0.042

gMVP

0.25

Mutation Taster

=98/2

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_032023.4:c.262A>G

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