Genetic Variant MAVS:c.-309C>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 NM_020746.5(MAVS):c.-309C>T variant causes a upstream gene 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
NM_020746.5 upstream_gene

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

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
MAVS	NM_020746.5 link	c.-309C>T	upstream_gene_variant	ENST00000428216.4	NP_065797.2	Q7Z434-1
MAVS	NM_001206491.2 link	c.-557C>T	upstream_gene_variant		NP_001193420.1	Q7Z434-4
MAVS	NM_001385663.1 link	c.-856C>T	upstream_gene_variant		NP_001372592.1
MAVS	NR_037921.2 link	n.-172C>T	upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAVS	ENST00000428216.4 link	c.-309C>T		upstream_gene_variant		1	NM_020746.5	ENSP00000401980.2		Q7Z434-1
MAVS	ENST00000416600.6 link	c.-557C>T		upstream_gene_variant		1		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 v4.3

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over