Variant 3-50331627-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_007182.5(RASSF1):c.692G>A(p.Arg231Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000739 in 1,605,538 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00049 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00077 ( 0 hom. )

Consequence

RASSF1
NM_007182.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.20

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11028516).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RASSF1	NM_007182.5 linkuse as main transcript	c.692G>A	p.Arg231Gln	missense_variant	4/6	ENST00000359365.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RASSF1	ENST00000359365.9 linkuse as main transcript	c.692G>A	p.Arg231Gln	missense_variant	4/6	1	NM_007182.5	P1	Q9NS23-2

Frequencies

GnomAD3 genomes

AF:

0.000493

AC:

AN:

152266

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000897

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000430

AC:

108

AN:

251038

Hom.:

AF XY:

0.000464

AC XY:

AN XY:

135742

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000203

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000416

Gnomad NFE exome

AF:

0.000723

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.000765

AC:

1112

AN:

1453154

Hom.:

Cov.:

AF XY:

0.000758

AC XY:

546

AN XY:

720770

show subpopulations

Gnomad4 AFR exome

AF:

0.0000601

Gnomad4 AMR exome

AF:

0.000292

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000395

Gnomad4 NFE exome

AF:

0.000930

Gnomad4 OTH exome

AF:

0.000801

GnomAD4 genome

AF:

0.000492

AC:

AN:

152384

Hom.:

Cov.:

AF XY:

0.000443

AC XY:

AN XY:

74518

show subpopulations

Gnomad4 AFR

AF:

0.000240

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000897

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000842

Hom.:

Bravo

AF:

0.000457

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.000930

AC:

ExAC

AF:

0.000420

AC:

EpiCase

AF:

0.000382

EpiControl

AF:

0.000948

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 16, 2021

The c.692G>A (p.R231Q) alteration is located in exon 4 (coding exon 4) of the RASSF1 gene. This alteration results from a G to A substitution at nucleotide position 692, causing the arginine (R) at amino acid position 231 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.50

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.12

.;.;.;T;.

Eigen

Benign

0.0066

Eigen_PC

Benign

0.12

FATHMM_MKL

Uncertain

0.81

LIST_S2

Pathogenic

0.98

D;D;.;D;D

M_CAP

Benign

0.021

MetaRNN

Benign

0.11

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.86

.;.;.;L;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Benign

0.48

PROVEAN

Benign

-1.6

N;.;N;N;N

REVEL

Benign

0.060

Sift

Uncertain

0.016

D;.;D;D;D

Sift4G

Uncertain

0.027

D;D;D;D;D

Polyphen

0.97, 0.76

.;.;.;D;P

Vest4

0.47

MVP

0.52

MPC

0.93

ClinPred

0.070

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.15

gMVP

0.39

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over