Genetic Variant MAVS:c.-68+3809C>T (chr20-3846662-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000972011.1(MAVS):c.-68+3809C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0667 in 152,256 control chromosomes in the GnomAD database, including 458 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 0.067 ( 458 hom., cov: 32)

Exomes 𝑓: 0.077 ( 0 hom. )

Consequence

MAVS
ENST00000972011.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.29

Publications

29 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

new If you want to explore the variant's impact on the transcript ENST00000972011.1, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000972011.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MAVS	NM_020746.5	MANE Select	c.-309C>T	upstream_gene	N/A	NP_065797.2	Q7Z434-1
MAVS	NM_001206491.2		c.-557C>T	upstream_gene	N/A	NP_001193420.1	Q7Z434-4
MAVS	NM_001385663.1		c.-856C>T	upstream_gene	N/A	NP_001372592.1	Q7Z434-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MAVS	ENST00000972011.1		c.-68+3809C>T	intron	N/A	ENSP00000642070.1
MAVS	ENST00000428216.4	TSL:1 MANE Select	c.-309C>T	upstream_gene	N/A	ENSP00000401980.2	Q7Z434-1
MAVS	ENST00000416600.6	TSL:1	c.-557C>T	upstream_gene	N/A	ENSP00000413749.2	Q7Z434-4

Frequencies

GnomAD3 genomes

AF:

0.0667

AC:

10149

AN:

152112

Hom.:

457

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0198

Gnomad AMI

AF:

0.162

Gnomad AMR

AF:

0.0568

Gnomad ASJ

AF:

0.0579

Gnomad EAS

AF:

0.00463

Gnomad SAS

AF:

0.0395

Gnomad FIN

AF:

0.0566

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.105

Gnomad OTH

AF:

0.0746

GnomAD4 exome

AF:

0.0769

AC:

AN:

Hom.:

AF XY:

0.0714

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0769

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0667

AC:

10149

AN:

152230

Hom.:

458

Cov.:

AF XY:

0.0636

AC XY:

4736

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.0197

AC:

819

AN:

41562

American (AMR)

AF:

0.0568

AC:

868

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0579

AC:

201

AN:

3472

East Asian (EAS)

AF:

0.00445

AC:

AN:

5168

South Asian (SAS)

AF:

0.0398

AC:

192

AN:

4830

European-Finnish (FIN)

AF:

0.0566

AC:

601

AN:

10610

Middle Eastern (MID)

AF:

0.0442

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.105

AC:

7125

AN:

67978

Other (OTH)

AF:

0.0752

AC:

159

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

502

1005

1507

2010

2512

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

118

236

354

472

590

<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:

0.0895

Hom.:

2224

Bravo

AF:

0.0644

Asia WGS

AF:

0.0360

AC:

124

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

1.6

(source)

DANN

Benign

0.88

PhyloP100

-1.3

PromoterAI

-0.037

Neutral

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over