dbSNP rs201825402: RASSF1:p.Arg247Leu (chr3-50331579-C-A) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_007182.5(RASSF1):c.740G>T(p.Arg247Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000693 in 1,443,722 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R247C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

RASSF1
NM_007182.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.18

Publications

2 publications found

Variant links:

Genes affected

RASSF1 (HGNC:9882): (Ras association domain family member 1) This gene encodes a protein similar to the RAS effector proteins. Loss or altered expression of this gene has been associated with the pathogenesis of a variety of cancers, which suggests the tumor suppressor function of this gene. The inactivation of this gene was found to be correlated with the hypermethylation of its CpG-island promoter region. The encoded protein was found to interact with DNA repair protein XPA. The protein was also shown to inhibit the accumulation of cyclin D1, and thus induce cell cycle arrest. Several alternatively spliced transcript variants of this gene encoding distinct isoforms have been reported. [provided by RefSeq, May 2011]

RASSF1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.816

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RASSF1	NM_007182.5 link	c.740G>T	p.Arg247Leu	missense_variant	Exon 4 of 6	ENST00000359365.9	NP_009113.3	Q9NS23-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RASSF1	ENST00000359365.9 link	c.740G>T	p.Arg247Leu	missense_variant	Exon 4 of 6	1	NM_007182.5	ENSP00000352323.4		Q9NS23-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000401

AC:

AN:

249066

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000889

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.93e-7

AC:

AN:

1443722

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

714078

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33144

American (AMR)

AF:

0.00

AC:

AN:

44222

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25808

East Asian (EAS)

AF:

0.00

AC:

AN:

39156

South Asian (SAS)

AF:

0.00

AC:

AN:

85782

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53022

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5728

European-Non Finnish (NFE)

AF:

9.11e-7

AC:

AN:

1097378

Other (OTH)

AF:

0.00

AC:

AN:

59482

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.43

BayesDel_addAF

Uncertain

0.045

BayesDel_noAF

Benign

-0.17

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.28

.;.;.;T;.

Eigen

Benign

0.066

Eigen_PC

Benign

0.050

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.93

D;D;.;D;D

M_CAP

Uncertain

0.11

MetaRNN

Pathogenic

0.82

D;D;D;D;D

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.7

.;.;.;M;.

PhyloP100

4.2

PrimateAI

Uncertain

0.71

PROVEAN

Pathogenic

-5.8

D;.;D;D;D

REVEL

Benign

0.24

Sift

Benign

0.071

T;.;D;D;T

Sift4G

Uncertain

0.043

D;D;D;T;T

Polyphen

1.0, 0.56

.;.;.;D;P

Vest4

0.86

MutPred

0.59

.;.;.;Gain of loop (P = 0.0435);.;

MVP

0.50

MPC

1.3

ClinPred

0.97

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.49

gMVP

0.75

Mutation Taster

=54/46

polymorphism

(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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over