Variant chr20-3864283-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_020746.5(MAVS):c.653G>A(p.Arg218His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000782 in 1,611,696 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000082 ( 0 hom. )

Consequence

MAVS
NM_020746.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.349

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 made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07402375).

BS2

High AC in GnomAd4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MAVS	NM_020746.5 linkuse as main transcript	c.653G>A	p.Arg218His	missense_variant	6/7	ENST00000428216.4
MAVS	NM_001206491.2 linkuse as main transcript	c.230G>A	p.Arg77His	missense_variant	5/6
MAVS	NM_001385663.1 linkuse as main transcript	c.230G>A	p.Arg77His	missense_variant	7/8
MAVS	NR_037921.2 linkuse as main transcript	n.617G>A		non_coding_transcript_exon_variant	5/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAVS	ENST00000428216.4 linkuse as main transcript	c.653G>A	p.Arg218His	missense_variant	6/7	1	NM_020746.5	P1	Q7Z434-1
MAVS	ENST00000416600.6 linkuse as main transcript	c.230G>A	p.Arg77His	missense_variant	5/6	1			Q7Z434-4

Frequencies

GnomAD3 genomes

AF:

0.0000395

AC:

AN:

152076

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.0000563

AC:

AN:

248634

Hom.:

AF XY:

0.0000223

AC XY:

AN XY:

134318

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.000175

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000446

Gnomad OTH exome

AF:

0.000330

GnomAD4 exome

AF:

0.0000822

AC:

120

AN:

1459620

Hom.:

Cov.:

AF XY:

0.0000703

AC XY:

AN XY:

725974

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000248

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000918

Gnomad4 OTH exome

AF:

0.0000995

GnomAD4 genome

AF:

0.0000395

AC:

AN:

152076

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74280

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.000956

Alfa

AF:

0.0000831

Hom.:

Bravo

AF:

0.0000756

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000412

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 12, 2022

The c.653G>A (p.R218H) alteration is located in exon 6 (coding exon 5) of the MAVS gene. This alteration results from a G to A substitution at nucleotide position 653, causing the arginine (R) at amino acid position 218 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.11

.;T

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.042

LIST_S2

Benign

0.78

T;T

M_CAP

Benign

0.0052

MetaRNN

Benign

0.074

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

.;L

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.25

PROVEAN

Uncertain

-2.6

D;N

REVEL

Benign

0.15

Sift

Benign

0.29

T;T

Sift4G

Benign

0.55

T;T

Polyphen

0.0070

.;B

Vest4

0.10

MVP

0.37

MPC

0.17

ClinPred

0.057

GERP RS

-0.69

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.023

gMVP

0.16

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over