Variant chr20-3865750-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 ENST00000428216.4(MAVS):c.1226C>T(p.Ser409Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 1,613,264 control chromosomes in the GnomAD database, including 23,993 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.21 ( 4161 hom., cov: 32)

Exomes 𝑓: 0.16 ( 19832 hom. )

Consequence

MAVS
ENST00000428216.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.503

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=0.0015271306).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.366 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.1226C>T	p.Ser409Phe	missense_variant	7/7	ENST00000428216.4	NP_065797.2	Q7Z434-1
MAVS	NM_001206491.2 linkuse as main transcript	c.803C>T	p.Ser268Phe	missense_variant	6/6		NP_001193420.1	Q7Z434-4
MAVS	NM_001385663.1 linkuse as main transcript	c.803C>T	p.Ser268Phe	missense_variant	8/8		NP_001372592.1
MAVS	NR_037921.2 linkuse as main transcript	n.1190C>T		non_coding_transcript_exon_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAVS	ENST00000428216.4 linkuse as main transcript	c.1226C>T	p.Ser409Phe	missense_variant	7/7	1	NM_020746.5	ENSP00000401980.2		Q7Z434-1
MAVS	ENST00000416600.6 linkuse as main transcript	c.803C>T	p.Ser268Phe	missense_variant	6/6	1		ENSP00000413749.2		Q7Z434-4

Frequencies

GnomAD3 genomes

AF:

0.210

AC:

31951

AN:

152004

Hom.:

4160

Cov.:

show subpopulations

Gnomad AFR

AF:

0.371

Gnomad AMI

AF:

0.0802

Gnomad AMR

AF:

0.154

Gnomad ASJ

AF:

0.157

Gnomad EAS

AF:

0.0850

Gnomad SAS

AF:

0.180

Gnomad FIN

AF:

0.109

Gnomad MID

AF:

0.193

Gnomad NFE

AF:

0.157

Gnomad OTH

AF:

0.212

GnomAD3 exomes

AF:

0.158

AC:

39437

AN:

249996

Hom.:

3728

AF XY:

0.157

AC XY:

21334

AN XY:

135528

show subpopulations

Gnomad AFR exome

AF:

0.372

Gnomad AMR exome

AF:

0.103

Gnomad ASJ exome

AF:

0.178

Gnomad EAS exome

AF:

0.0972

Gnomad SAS exome

AF:

0.177

Gnomad FIN exome

AF:

0.113

Gnomad NFE exome

AF:

0.155

Gnomad OTH exome

AF:

0.168

GnomAD4 exome

AF:

0.158

AC:

230872

AN:

1461142

Hom.:

19832

Cov.:

AF XY:

0.159

AC XY:

115386

AN XY:

726880

show subpopulations

Gnomad4 AFR exome

AF:

0.379

Gnomad4 AMR exome

AF:

0.108

Gnomad4 ASJ exome

AF:

0.168

Gnomad4 EAS exome

AF:

0.105

Gnomad4 SAS exome

AF:

0.177

Gnomad4 FIN exome

AF:

0.115

Gnomad4 NFE exome

AF:

0.155

Gnomad4 OTH exome

AF:

0.169

GnomAD4 genome

AF:

0.210

AC:

31981

AN:

152122

Hom.:

4161

Cov.:

AF XY:

0.205

AC XY:

15254

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.371

Gnomad4 AMR

AF:

0.154

Gnomad4 ASJ

AF:

0.157

Gnomad4 EAS

AF:

0.0850

Gnomad4 SAS

AF:

0.180

Gnomad4 FIN

AF:

0.109

Gnomad4 NFE

AF:

0.157

Gnomad4 OTH

AF:

0.211

Alfa

AF:

0.166

Hom.:

4458

Bravo

AF:

0.219

TwinsUK

AF:

0.162

AC:

601

ALSPAC

AF:

0.137

AC:

528

ESP6500AA

AF:

0.359

AC:

1581

ESP6500EA

AF:

0.162

AC:

1393

ExAC

AF:

0.164

AC:

19860

Asia WGS

AF:

0.146

AC:

509

AN:

3478

EpiCase

AF:

0.161

EpiControl

AF:

0.161

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.40

.;T

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.62

FATHMM_MKL

Benign

0.096

LIST_S2

Benign

0.57

T;T

MetaRNN

Benign

0.0015

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

.;L

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-4.3

D;N

REVEL

Benign

0.054

Sift

Benign

0.24

T;T

Sift4G

Uncertain

0.024

D;D

Polyphen

0.99

.;D

Vest4

0.093

MPC

0.20

ClinPred

0.058

GERP RS

0.17

Varity_R

0.069

gMVP

0.13

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