Variant 20-3864282-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_020746.5(MAVS):c.652C>T(p.Arg218Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 1,611,608 control chromosomes in the GnomAD database, including 16,102 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.11 ( 1105 hom., cov: 32)

Exomes 𝑓: 0.14 ( 14997 hom. )

Consequence

MAVS
NM_020746.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.931

Variant links:

Genes affected

MAVS (HGNC:29233): (mitochondrial antiviral signaling protein) This gene encodes an intermediary protein necessary in the virus-triggered beta interferon signaling pathways. It is required for activation of transcription factors which regulate expression of beta interferon and contributes to antiviral innate immunity. [provided by RefSeq, Jul 2020]

MAVS links:

MAVS (HGNC:):

MAVS links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014338195).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAVS	NM_020746.5 linkuse as main transcript	c.652C>T	p.Arg218Cys	missense_variant	6/7	ENST00000428216.4	NP_065797.2	Q7Z434-1
MAVS	NM_001206491.2 linkuse as main transcript	c.229C>T	p.Arg77Cys	missense_variant	5/6		NP_001193420.1	Q7Z434-4
MAVS	NM_001385663.1 linkuse as main transcript	c.229C>T	p.Arg77Cys	missense_variant	7/8		NP_001372592.1
MAVS	NR_037921.2 linkuse as main transcript	n.616C>T		non_coding_transcript_exon_variant	5/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAVS	ENST00000428216.4 linkuse as main transcript	c.652C>T	p.Arg218Cys	missense_variant	6/7	1	NM_020746.5	ENSP00000401980.2		Q7Z434-1
MAVS	ENST00000416600.6 linkuse as main transcript	c.229C>T	p.Arg77Cys	missense_variant	5/6	1		ENSP00000413749.2		Q7Z434-4

Frequencies

GnomAD3 genomes

AF:

0.105

AC:

16001

AN:

152048

Hom.:

1105

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0285

Gnomad AMI

AF:

0.184

Gnomad AMR

AF:

0.110

Gnomad ASJ

AF:

0.150

Gnomad EAS

AF:

0.00193

Gnomad SAS

AF:

0.0344

Gnomad FIN

AF:

0.108

Gnomad MID

AF:

0.139

Gnomad NFE

AF:

0.159

Gnomad OTH

AF:

0.127

GnomAD3 exomes

AF:

0.109

AC:

27058

AN:

248682

Hom.:

1926

AF XY:

0.110

AC XY:

14769

AN XY:

134332

show subpopulations

Gnomad AFR exome

AF:

0.0264

Gnomad AMR exome

AF:

0.0785

Gnomad ASJ exome

AF:

0.142

Gnomad EAS exome

AF:

0.00131

Gnomad SAS exome

AF:

0.0354

Gnomad FIN exome

AF:

0.112

Gnomad NFE exome

AF:

0.162

Gnomad OTH exome

AF:

0.144

GnomAD4 exome

AF:

0.136

AC:

198980

AN:

1459442

Hom.:

14997

Cov.:

AF XY:

0.135

AC XY:

97700

AN XY:

725846

show subpopulations

Gnomad4 AFR exome

AF:

0.0251

Gnomad4 AMR exome

AF:

0.0830

Gnomad4 ASJ exome

AF:

0.142

Gnomad4 EAS exome

AF:

0.00103

Gnomad4 SAS exome

AF:

0.0371

Gnomad4 FIN exome

AF:

0.112

Gnomad4 NFE exome

AF:

0.156

Gnomad4 OTH exome

AF:

0.127

GnomAD4 genome

AF:

0.105

AC:

15996

AN:

152166

Hom.:

1105

Cov.:

AF XY:

0.102

AC XY:

7551

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.0284

Gnomad4 AMR

AF:

0.110

Gnomad4 ASJ

AF:

0.150

Gnomad4 EAS

AF:

0.00193

Gnomad4 SAS

AF:

0.0346

Gnomad4 FIN

AF:

0.108

Gnomad4 NFE

AF:

0.159

Gnomad4 OTH

AF:

0.125

Alfa

AF:

0.145

Hom.:

2727

Bravo

AF:

0.103

TwinsUK

AF:

0.138

AC:

513

ALSPAC

AF:

0.144

AC:

556

ESP6500AA

AF:

0.0384

AC:

169

ESP6500EA

AF:

0.165

AC:

1418

ExAC

AF:

0.110

AC:

13311

Asia WGS

AF:

0.0180

AC:

AN:

3478

EpiCase

AF:

0.168

EpiControl

AF:

0.167

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.70

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.17

.;T

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.026

LIST_S2

Benign

0.82

T;T

MetaRNN

Benign

0.0014

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.0

.;M

PrimateAI

Benign

0.26

PROVEAN

Pathogenic

-5.1

D;D

REVEL

Benign

0.035

Sift

Benign

0.14

T;T

Sift4G

Benign

0.20

T;T

Polyphen

0.015

.;B

Vest4

0.17

MPC

0.19

ClinPred

0.041

GERP RS

0.35

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.085

gMVP

0.20

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