Variant 7-4800182-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_018059.5(RADIL):c.2971A>G(p.Ile991Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000727 in 1,608,866 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000071 ( 1 hom. )

Consequence

RADIL
NM_018059.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.74

Variant links:

Genes affected

RADIL (HGNC:22226): (Rap associating with DIL domain) Predicted to enable GTPase binding activity. Acts upstream of or within substrate adhesion-dependent cell spreading. Located in microtubule. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

RADIL links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.027090311).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RADIL	NM_018059.5 link	c.2971A>G	p.Ile991Val	missense_variant	13/15	ENST00000399583.4	NP_060529.4	Q96JH8-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RADIL	ENST00000399583.4 link	c.2971A>G	p.Ile991Val	missense_variant	13/15	5	NM_018059.5	ENSP00000382492.3		Q96JH8-4

Frequencies

GnomAD3 genomes

AF:

0.0000920

AC:

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000163

AC:

AN:

238632

Hom.:

AF XY:

0.000176

AC XY:

AN XY:

130648

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000103

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000334

Gnomad FIN exome

AF:

0.000767

Gnomad NFE exome

AF:

0.000195

Gnomad OTH exome

AF:

0.000173

GnomAD4 exome

AF:

0.0000707

AC:

103

AN:

1456622

Hom.:

Cov.:

AF XY:

0.0000814

AC XY:

AN XY:

724574

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000385

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.000664

Gnomad4 NFE exome

AF:

0.0000495

Gnomad4 OTH exome

AF:

0.000166

GnomAD4 genome

AF:

0.0000920

AC:

AN:

152244

Hom.:

Cov.:

AF XY:

0.0000806

AC XY:

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000149

Hom.:

Bravo

AF:

0.0000491

ExAC

AF:

0.000158

AC:

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 09, 2024

The c.2971A>G (p.I991V) alteration is located in exon 13 (coding exon 12) of the RADIL gene. This alteration results from a A to G substitution at nucleotide position 2971, causing the isoleucine (I) at amino acid position 991 to be replaced by a valine (V). 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

-0.47

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.85

DEOGEN2

Benign

0.0097

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.60

LIST_S2

Benign

0.82

M_CAP

Benign

0.014

MetaRNN

Benign

0.027

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-1.1

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-0.35

REVEL

Benign

0.027

Sift

Benign

0.22

Sift4G

Benign

0.57

Polyphen

0.0010

Vest4

0.17

MVP

0.12

MPC

0.042

ClinPred

0.021

GERP RS

0.35

Varity_R

0.031

gMVP

0.31

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