Variant 20-3857794-C-G 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.277C>G(p.Gln93Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 1,613,994 control chromosomes in the GnomAD database, including 59,318 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 0.23 ( 4812 hom., cov: 32)

Exomes 𝑓: 0.27 ( 54506 hom. )

Consequence

MAVS
NM_020746.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.220

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=6.158712E-5).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.562 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.277C>G	p.Gln93Glu	missense_variant	3/7	ENST00000428216.4	NP_065797.2	Q7Z434-1
MAVS	NM_001385663.1 linkuse as main transcript	c.-271C>G		5_prime_UTR_variant	3/8		NP_001372592.1
MAVS	NM_001206491.2 linkuse as main transcript	c.-132+3053C>G		intron_variant			NP_001193420.1	Q7Z434-4
MAVS	NR_037921.2 linkuse as main transcript	n.414C>G		non_coding_transcript_exon_variant	3/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAVS	ENST00000428216.4 linkuse as main transcript	c.277C>G	p.Gln93Glu	missense_variant	3/7	1	NM_020746.5	ENSP00000401980.2		Q7Z434-1
MAVS	ENST00000416600.6 linkuse as main transcript	c.-132+3053C>G		intron_variant		1		ENSP00000413749.2		Q7Z434-4

Frequencies

GnomAD3 genomes

AF:

0.230

AC:

34921

AN:

152074

Hom.:

4810

Cov.:

show subpopulations

Gnomad AFR

AF:

0.102

Gnomad AMI

AF:

0.263

Gnomad AMR

AF:

0.269

Gnomad ASJ

AF:

0.247

Gnomad EAS

AF:

0.580

Gnomad SAS

AF:

0.315

Gnomad FIN

AF:

0.265

Gnomad MID

AF:

0.253

Gnomad NFE

AF:

0.258

Gnomad OTH

AF:

0.248

GnomAD3 exomes

AF:

0.286

AC:

71842

AN:

251358

Hom.:

11651

AF XY:

0.290

AC XY:

39395

AN XY:

135860

show subpopulations

Gnomad AFR exome

AF:

0.0988

Gnomad AMR exome

AF:

0.295

Gnomad ASJ exome

AF:

0.252

Gnomad EAS exome

AF:

0.574

Gnomad SAS exome

AF:

0.330

Gnomad FIN exome

AF:

0.267

Gnomad NFE exome

AF:

0.259

Gnomad OTH exome

AF:

0.263

GnomAD4 exome

AF:

0.265

AC:

387488

AN:

1461802

Hom.:

54506

Cov.:

AF XY:

0.267

AC XY:

194468

AN XY:

727204

show subpopulations

Gnomad4 AFR exome

AF:

0.0955

Gnomad4 AMR exome

AF:

0.293

Gnomad4 ASJ exome

AF:

0.242

Gnomad4 EAS exome

AF:

0.561

Gnomad4 SAS exome

AF:

0.325

Gnomad4 FIN exome

AF:

0.267

Gnomad4 NFE exome

AF:

0.254

Gnomad4 OTH exome

AF:

0.268

GnomAD4 genome

AF:

0.229

AC:

34924

AN:

152192

Hom.:

4812

Cov.:

AF XY:

0.235

AC XY:

17469

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.103

Gnomad4 AMR

AF:

0.269

Gnomad4 ASJ

AF:

0.247

Gnomad4 EAS

AF:

0.580

Gnomad4 SAS

AF:

0.313

Gnomad4 FIN

AF:

0.265

Gnomad4 NFE

AF:

0.258

Gnomad4 OTH

AF:

0.245

Alfa

AF:

0.247

Hom.:

3790

Bravo

AF:

0.226

TwinsUK

AF:

0.261

AC:

968

ALSPAC

AF:

0.255

AC:

981

ESP6500AA

AF:

0.103

AC:

452

ESP6500EA

AF:

0.248

AC:

2136

ExAC

AF:

0.280

AC:

34012

Asia WGS

AF:

0.393

AC:

1366

AN:

3478

EpiCase

AF:

0.254

EpiControl

AF:

0.259

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.11

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.30

FATHMM_MKL

Benign

0.028

LIST_S2

Benign

0.72

MetaRNN

Benign

0.000062

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.2

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.51

REVEL

Benign

0.031

Sift

Benign

0.079

Sift4G

Uncertain

0.050

Polyphen

0.88

Vest4

0.069

MPC

0.18

ClinPred

0.010

GERP RS

2.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.29

gMVP

0.11

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