Genetic Variant MAVS:p.Cys79Phe (chr20-3857753-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_020746.5(MAVS):c.236G>T(p.Cys79Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00696 in 1,614,194 control chromosomes in the GnomAD database, including 630 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.036 ( 325 hom., cov: 33)

Exomes 𝑓: 0.0039 ( 305 hom. )

Consequence

MAVS
NM_020746.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.26

Publications

28 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0034611523).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAVS	NM_020746.5 link	c.236G>T	p.Cys79Phe	missense_variant	Exon 3 of 7	ENST00000428216.4	NP_065797.2	Q7Z434-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAVS	ENST00000428216.4 link	c.236G>T	p.Cys79Phe	missense_variant	Exon 3 of 7	1	NM_020746.5	ENSP00000401980.2		Q7Z434-1
MAVS	ENST00000416600.6 link	c.-132+3012G>T		intron_variant	Intron 2 of 5	1		ENSP00000413749.2		Q7Z434-4

Frequencies

GnomAD3 genomes

AF:

0.0364

AC:

5544

AN:

152190

Hom.:

324

Cov.:

show subpopulations

Gnomad AFR

AF:

0.126

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0135

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000376

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000500

Gnomad OTH

AF:

0.0354

GnomAD2 exomes

AF:

0.00971

AC:

2442

AN:

251478

AF XY:

0.00686

show subpopulations

Gnomad AFR exome

AF:

0.128

Gnomad AMR exome

AF:

0.00700

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000785

Gnomad NFE exome

AF:

0.000527

Gnomad OTH exome

AF:

0.00537

GnomAD4 exome

AF:

0.00389

AC:

5685

AN:

1461886

Hom.:

305

Cov.:

AF XY:

0.00339

AC XY:

2463

AN XY:

727240

show subpopulations

African (AFR)

AF:

0.133

AC:

4445

AN:

33478

American (AMR)

AF:

0.00789

AC:

353

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000243

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.000693

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00607

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000248

AC:

276

AN:

1112008

Other (OTH)

AF:

0.00856

AC:

517

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.452

Heterozygous variant carriers

304

609

913

1218

1522

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

132

264

396

528

660

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0364

AC:

5549

AN:

152308

Hom.:

325

Cov.:

AF XY:

0.0346

AC XY:

2574

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.126

AC:

5226

AN:

41540

American (AMR)

AF:

0.0135

AC:

206

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.000207

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.000376

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000500

AC:

AN:

68036

Other (OTH)

AF:

0.0350

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

237

475

712

950

1187

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

150

200

250

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0138

Hom.:

292

Bravo

AF:

0.0423

ESP6500AA

AF:

0.00363

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0115

AC:

1400

Asia WGS

AF:

0.00491

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000652

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.82

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Uncertain

0.020

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.27

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.76

MetaRNN

Benign

0.0035

MetaSVM

Benign

-1.2

MutationAssessor

Benign

1.1

PhyloP100

4.3

PrimateAI

Benign

0.47

PROVEAN

Pathogenic

-7.4

REVEL

Uncertain

0.29

Sift

Uncertain

0.0030

Sift4G

Benign

0.17

Polyphen

1.0

Vest4

0.36

MPC

0.24

ClinPred

0.084

GERP RS

4.7

Varity_R

0.88

gMVP

0.54

Mutation Taster

=93/7

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over