Variant rs677688 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_018439.4(IMPACT):c.451C>G(p.Leu151Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.914 in 1,612,828 control chromosomes in the GnomAD database, including 675,851 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.92 ( 64597 hom., cov: 33)

Exomes 𝑓: 0.91 ( 611254 hom. )

Consequence

IMPACT
NM_018439.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.698

Variant links:

Genes affected

IMPACT (HGNC:20387): (impact RWD domain protein) Predicted to enable actin binding activity and ribosome binding activity. Predicted to be involved in several processes, including GCN2-mediated signaling; cellular response to starvation; and negative regulation of nitrogen compound metabolic process. Predicted to be located in cytoplasm. Predicted to be part of polysome. [provided by Alliance of Genome Resources, Apr 2022]

IMPACT links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.073872E-6).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.939 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IMPACT	NM_018439.4 linkuse as main transcript	c.451C>G	p.Leu151Val	missense_variant	6/11	ENST00000284202.9	NP_060909.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IMPACT	ENST00000284202.9 linkuse as main transcript	c.451C>G	p.Leu151Val	missense_variant	6/11	1	NM_018439.4	ENSP00000284202	P1	Q9P2X3-1

Frequencies

GnomAD3 genomes

AF:

0.920

AC:

139934

AN:

152164

Hom.:

64539

Cov.:

show subpopulations

Gnomad AFR

AF:

0.935

Gnomad AMI

AF:

0.918

Gnomad AMR

AF:

0.952

Gnomad ASJ

AF:

0.937

Gnomad EAS

AF:

0.677

Gnomad SAS

AF:

0.867

Gnomad FIN

AF:

0.932

Gnomad MID

AF:

0.905

Gnomad NFE

AF:

0.923

Gnomad OTH

AF:

0.915

GnomAD3 exomes

AF:

0.906

AC:

226974

AN:

250564

Hom.:

103618

AF XY:

0.903

AC XY:

122301

AN XY:

135442

show subpopulations

Gnomad AFR exome

AF:

0.935

Gnomad AMR exome

AF:

0.970

Gnomad ASJ exome

AF:

0.941

Gnomad EAS exome

AF:

0.662

Gnomad SAS exome

AF:

0.873

Gnomad FIN exome

AF:

0.928

Gnomad NFE exome

AF:

0.923

Gnomad OTH exome

AF:

0.915

GnomAD4 exome

AF:

0.914

AC:

1334535

AN:

1460546

Hom.:

611254

Cov.:

AF XY:

0.913

AC XY:

663143

AN XY:

726622

show subpopulations

Gnomad4 AFR exome

AF:

0.939

Gnomad4 AMR exome

AF:

0.968

Gnomad4 ASJ exome

AF:

0.942

Gnomad4 EAS exome

AF:

0.690

Gnomad4 SAS exome

AF:

0.876

Gnomad4 FIN exome

AF:

0.928

Gnomad4 NFE exome

AF:

0.920

Gnomad4 OTH exome

AF:

0.910

GnomAD4 genome

AF:

0.920

AC:

140053

AN:

152282

Hom.:

64597

Cov.:

AF XY:

0.918

AC XY:

68374

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.935

Gnomad4 AMR

AF:

0.952

Gnomad4 ASJ

AF:

0.937

Gnomad4 EAS

AF:

0.677

Gnomad4 SAS

AF:

0.868

Gnomad4 FIN

AF:

0.932

Gnomad4 NFE

AF:

0.923

Gnomad4 OTH

AF:

0.911

Alfa

AF:

0.918

Hom.:

48412

Bravo

AF:

0.922

TwinsUK

AF:

0.913

AC:

3387

ALSPAC

AF:

0.915

AC:

3528

ESP6500AA

AF:

0.935

AC:

4120

ESP6500EA

AF:

0.922

AC:

7929

ExAC

AF:

0.903

AC:

109679

Asia WGS

AF:

0.772

AC:

2684

AN:

3478

EpiCase

AF:

0.929

EpiControl

AF:

0.925

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.049

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.64

CADD

Benign

2.8

DANN

Benign

0.48

DEOGEN2

Benign

0.012

T;.;T;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.00067

LIST_S2

Benign

0.046

T;T;T;T

MetaRNN

Benign

0.0000011

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.8

N;.;.;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.33

PROVEAN

Benign

0.27

N;.;.;.

REVEL

Benign

0.017

Sift

Benign

0.78

T;.;.;.

Sift4G

Benign

1.0

T;.;T;T

Polyphen

0.0

B;.;.;.

Vest4

0.016

MPC

0.063

ClinPred

0.00027

GERP RS

2.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.020

gMVP

0.15

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over