Variant 10-44984028-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_032023.4(RASSF4):c.288G>T(p.Glu96Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.003 in 1,598,326 control chromosomes in the GnomAD database, including 109 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 64 hom., cov: 33)

Exomes 𝑓: 0.0017 ( 45 hom. )

Consequence

RASSF4
NM_032023.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.417

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 made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017531216).

BP6

Variant 10-44984028-G-T is Benign according to our data. Variant chr10-44984028-G-T is described in ClinVar as [Benign]. Clinvar id is 780862.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0149 (2272/152324) while in subpopulation AFR AF= 0.0499 (2076/41564). AF 95% confidence interval is 0.0482. There are 64 homozygotes in gnomad4. There are 1034 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 64 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RASSF4	NM_032023.4 linkuse as main transcript	c.288G>T	p.Glu96Asp	missense_variant	5/11	ENST00000340258.10	NP_114412.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RASSF4	ENST00000340258.10 linkuse as main transcript	c.288G>T	p.Glu96Asp	missense_variant	5/11	1	NM_032023.4	ENSP00000339692	P1	Q9H2L5-1

Frequencies

GnomAD3 genomes

AF:

0.0149

AC:

2262

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0499

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00805

Gnomad ASJ

AF:

0.00547

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.000353

Gnomad OTH

AF:

0.0110

GnomAD3 exomes

AF:

0.00371

AC:

834

AN:

224536

Hom.:

AF XY:

0.00291

AC XY:

352

AN XY:

120978

show subpopulations

Gnomad AFR exome

AF:

0.0451

Gnomad AMR exome

AF:

0.00392

Gnomad ASJ exome

AF:

0.00403

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000739

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000350

Gnomad OTH exome

AF:

0.00284

GnomAD4 exome

AF:

0.00174

AC:

2516

AN:

1446002

Hom.:

Cov.:

AF XY:

0.00159

AC XY:

1141

AN XY:

717646

show subpopulations

Gnomad4 AFR exome

AF:

0.0514

Gnomad4 AMR exome

AF:

0.00422

Gnomad4 ASJ exome

AF:

0.00438

Gnomad4 EAS exome

AF:

0.0000512

Gnomad4 SAS exome

AF:

0.000156

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000184

Gnomad4 OTH exome

AF:

0.00450

GnomAD4 genome

AF:

0.0149

AC:

2272

AN:

152324

Hom.:

Cov.:

AF XY:

0.0139

AC XY:

1034

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.0499

Gnomad4 AMR

AF:

0.00804

Gnomad4 ASJ

AF:

0.00547

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000353

Gnomad4 OTH

AF:

0.0109

Alfa

AF:

0.00768

Hom.:

Bravo

AF:

0.0176

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0493

AC:

217

ESP6500EA

AF:

0.000582

AC:

ExAC

AF:

0.00424

AC:

514

Asia WGS

AF:

0.00346

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 09, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.60

CADD

Benign

5.2

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0021

T;T

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.082

LIST_S2

Benign

0.42

T;T

MetaRNN

Benign

0.0018

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

L;.

MutationTaster

Benign

1.0

D;N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.83

N;N

REVEL

Benign

0.093

Sift

Benign

0.35

T;T

Sift4G

Benign

0.59

T;T

Polyphen

0.0020

B;.

Vest4

0.19

MutPred

0.15

Loss of helix (P = 0.0444);.;

MVP

0.34

MPC

0.090

ClinPred

0.0090

GERP RS

0.94

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.067

gMVP

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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