Variant 20-3865761-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_020746.5(MAVS):c.1237G>A(p.Gly413Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00159 in 1,613,660 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0084 ( 16 hom., cov: 33)

Exomes 𝑓: 0.00088 ( 16 hom. )

Consequence

MAVS
NM_020746.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0490

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 Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0034693182).

BP6

Variant 20-3865761-G-A is Benign according to our data. Variant chr20-3865761-G-A is described in ClinVar as [Benign]. Clinvar id is 769074.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00844 (1286/152308) while in subpopulation AFR AF= 0.0298 (1239/41572). AF 95% confidence interval is 0.0284. There are 16 homozygotes in gnomad4. There are 613 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1286 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MAVS	NM_020746.5 linkuse as main transcript	c.1237G>A	p.Gly413Ser	missense_variant	7/7	ENST00000428216.4
MAVS	NM_001206491.2 linkuse as main transcript	c.814G>A	p.Gly272Ser	missense_variant	6/6
MAVS	NM_001385663.1 linkuse as main transcript	c.814G>A	p.Gly272Ser	missense_variant	8/8
MAVS	NR_037921.2 linkuse as main transcript	n.1201G>A		non_coding_transcript_exon_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAVS	ENST00000428216.4 linkuse as main transcript	c.1237G>A	p.Gly413Ser	missense_variant	7/7	1	NM_020746.5	P1	Q7Z434-1
MAVS	ENST00000416600.6 linkuse as main transcript	c.814G>A	p.Gly272Ser	missense_variant	6/6	1			Q7Z434-4

Frequencies

GnomAD3 genomes

AF:

0.00837

AC:

1274

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0296

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00229

Gnomad ASJ

AF:

0.000288

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:

0.00478

GnomAD3 exomes

AF:

0.00228

AC:

570

AN:

250524

Hom.:

AF XY:

0.00159

AC XY:

216

AN XY:

135690

show subpopulations

Gnomad AFR exome

AF:

0.0313

Gnomad AMR exome

AF:

0.00136

Gnomad ASJ exome

AF:

0.000199

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000619

Gnomad OTH exome

AF:

0.000818

GnomAD4 exome

AF:

0.000878

AC:

1283

AN:

1461352

Hom.:

Cov.:

AF XY:

0.000763

AC XY:

555

AN XY:

726988

show subpopulations

Gnomad4 AFR exome

AF:

0.0298

Gnomad4 AMR exome

AF:

0.00183

Gnomad4 ASJ exome

AF:

0.000344

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000209

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000153

Gnomad4 OTH exome

AF:

0.00245

GnomAD4 genome

AF:

0.00844

AC:

1286

AN:

152308

Hom.:

Cov.:

AF XY:

0.00823

AC XY:

613

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.0298

Gnomad4 AMR

AF:

0.00216

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00168

Hom.:

Bravo

AF:

0.00941

ESP6500AA

AF:

0.0284

AC:

125

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00276

AC:

335

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Apr 06, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.72

CADD

Benign

3.2

DANN

Benign

0.65

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.053

LIST_S2

Benign

0.47

T;T

MetaRNN

Benign

0.0035

T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.9

N;N

REVEL

Benign

0.037

Sift

Benign

0.34

T;T

Sift4G

Benign

0.76

T;T

Polyphen

0.12

.;B

Vest4

0.041

MVP

0.41

MPC

0.13

ClinPred

0.0036

GERP RS

-0.43

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.022

gMVP

0.075

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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