Variant 20-3866015-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_020746.5(MAVS):c.1491C>T(p.Ala497=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00793 in 1,612,878 control chromosomes in the GnomAD database, including 85 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 17 hom., cov: 33)

Exomes 𝑓: 0.0077 ( 68 hom. )

Consequence

MAVS
NM_020746.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -3.05

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 20-3866015-C-T is Benign according to our data. Variant chr20-3866015-C-T is described in ClinVar as [Benign]. Clinvar id is 771779.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.05 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0105 (1606/152288) while in subpopulation AFR AF= 0.0201 (834/41572). AF 95% confidence interval is 0.0189. There are 17 homozygotes in gnomad4. There are 769 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1606 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MAVS	NM_020746.5 linkuse as main transcript	c.1491C>T	p.Ala497=	synonymous_variant	7/7	ENST00000428216.4
MAVS	NM_001206491.2 linkuse as main transcript	c.1068C>T	p.Ala356=	synonymous_variant	6/6
MAVS	NM_001385663.1 linkuse as main transcript	c.1068C>T	p.Ala356=	synonymous_variant	8/8
MAVS	NR_037921.2 linkuse as main transcript	n.1455C>T		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.1491C>T	p.Ala497=	synonymous_variant	7/7	1	NM_020746.5	P1	Q7Z434-1
MAVS	ENST00000416600.6 linkuse as main transcript	c.1068C>T	p.Ala356=	synonymous_variant	6/6	1			Q7Z434-4

Frequencies

GnomAD3 genomes

AF:

0.0105

AC:

1603

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0200

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.00517

Gnomad ASJ

AF:

0.00720

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.00235

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00864

Gnomad OTH

AF:

0.0153

GnomAD3 exomes

AF:

0.00732

AC:

1812

AN:

247642

Hom.:

AF XY:

0.00684

AC XY:

922

AN XY:

134758

show subpopulations

Gnomad AFR exome

AF:

0.0219

Gnomad AMR exome

AF:

0.00611

Gnomad ASJ exome

AF:

0.00612

Gnomad EAS exome

AF:

0.0000547

Gnomad SAS exome

AF:

0.00248

Gnomad FIN exome

AF:

0.00251

Gnomad NFE exome

AF:

0.00906

Gnomad OTH exome

AF:

0.00940

GnomAD4 exome

AF:

0.00766

AC:

11181

AN:

1460590

Hom.:

Cov.:

AF XY:

0.00760

AC XY:

5522

AN XY:

726634

show subpopulations

Gnomad4 AFR exome

AF:

0.0221

Gnomad4 AMR exome

AF:

0.00653

Gnomad4 ASJ exome

AF:

0.00551

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00291

Gnomad4 FIN exome

AF:

0.00199

Gnomad4 NFE exome

AF:

0.00811

Gnomad4 OTH exome

AF:

0.00924

GnomAD4 genome

AF:

0.0105

AC:

1606

AN:

152288

Hom.:

Cov.:

AF XY:

0.0103

AC XY:

769

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.0201

Gnomad4 AMR

AF:

0.00517

Gnomad4 ASJ

AF:

0.00720

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00269

Gnomad4 FIN

AF:

0.00235

Gnomad4 NFE

AF:

0.00865

Gnomad4 OTH

AF:

0.0151

Alfa

AF:

0.00635

Hom.:

Bravo

AF:

0.0111

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.00960

EpiControl

AF:

0.00901

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 20, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

1.2

DANN

Benign

0.42

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over