Genetic Variant NM_032023.4:c.807+58G>A (chr10-44991127-G-A) – 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.807+58G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0502 in 1,527,448 control chromosomes in the GnomAD database, including 2,845 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 0.041 ( 208 hom., cov: 33)

Exomes 𝑓: 0.051 ( 2637 hom. )

Consequence

RASSF4
NM_032023.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.01

Publications

2 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:

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 (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032023.4. 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
	RASSF4	NM_032023.4	MANE Select	c.807+58G>A		intron	N/A	NP_114412.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
RASSF4	ENST00000340258.10	TSL:1 MANE Select	c.807+58G>A	intron	N/A	ENSP00000339692.4
RASSF4	ENST00000489171.5	TSL:1	n.2813+58G>A	intron	N/A
RASSF4	ENST00000484477.2	TSL:2	c.*22G>A	3_prime_UTR	Exon 3 of 3	ENSP00000476848.1

Frequencies

GnomAD3 genomes

AF:

0.0414

AC:

6292

AN:

152094

Hom.:

210

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0101

Gnomad AMI

AF:

0.0879

Gnomad AMR

AF:

0.0373

Gnomad ASJ

AF:

0.0314

Gnomad EAS

AF:

0.151

Gnomad SAS

AF:

0.165

Gnomad FIN

AF:

0.0371

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0447

Gnomad OTH

AF:

0.0441

GnomAD2 exomes

AF:

0.0632

AC:

12892

AN:

203962

AF XY:

0.0680

show subpopulations

Gnomad AFR exome

AF:

0.00924

Gnomad AMR exome

AF:

0.0288

Gnomad ASJ exome

AF:

0.0363

Gnomad EAS exome

AF:

0.163

Gnomad FIN exome

AF:

0.0402

Gnomad NFE exome

AF:

0.0445

Gnomad OTH exome

AF:

0.0579

GnomAD4 exome

AF:

0.0512

AC:

70413

AN:

1375236

Hom.:

2637

Cov.:

AF XY:

0.0540

AC XY:

36655

AN XY:

679102

show subpopulations

African (AFR)

AF:

0.00680

AC:

213

AN:

31322

American (AMR)

AF:

0.0281

AC:

1072

AN:

38166

Ashkenazi Jewish (ASJ)

AF:

0.0359

AC:

834

AN:

23248

East Asian (EAS)

AF:

0.141

AC:

5450

AN:

38594

South Asian (SAS)

AF:

0.149

AC:

11774

AN:

78876

European-Finnish (FIN)

AF:

0.0403

AC:

1707

AN:

42310

Middle Eastern (MID)

AF:

0.0301

AC:

141

AN:

4678

European-Non Finnish (NFE)

AF:

0.0435

AC:

46139

AN:

1061354

Other (OTH)

AF:

0.0544

AC:

3083

AN:

56688

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

2929

5857

8786

11714

14643

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1930

3860

5790

7720

9650

<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:

0.0413

AC:

6284

AN:

152212

Hom.:

208

Cov.:

AF XY:

0.0441

AC XY:

3279

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.0101

AC:

420

AN:

41552

American (AMR)

AF:

0.0373

AC:

570

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0314

AC:

109

AN:

3468

East Asian (EAS)

AF:

0.150

AC:

774

AN:

5152

South Asian (SAS)

AF:

0.164

AC:

788

AN:

4814

European-Finnish (FIN)

AF:

0.0371

AC:

393

AN:

10606

Middle Eastern (MID)

AF:

0.0476

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0448

AC:

3044

AN:

68010

Other (OTH)

AF:

0.0436

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

297

595

892

1190

1487

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

152

228

304

380

<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:

0.0403

Hom.:

Bravo

AF:

0.0376

Asia WGS

AF:

0.141

AC:

488

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.30

(source)

DANN

Benign

0.52

PhyloP100

-1.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over