20-3857794-C-G

Variant names:

• chr20-3857794-C-G
• rs17857295
• NM_020746.5:c.277C>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020746.5(MAVS):​c.277C>G​(p.Gln93Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 1,613,994 control chromosomes in the GnomAD database, including 59,318 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.23 (4812 hom., cov: 32)
  • Exomes 𝑓: 0.27 (54506 hom.)
• Consequence: MAVS NM_020746.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.220

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=6.158712E-5).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.562 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAVS	NM_020746.5	c.277C>G	p.Gln93Glu	missense_variant	Exon 3 of 7	ENST00000428216.4	NP_065797.2
MAVS	NM_001385663.1	c.-271C>G		5_prime_UTR_variant	Exon 3 of 8		NP_001372592.1
MAVS	NM_001206491.2	c.-132+3053C>G		intron_variant	Intron 2 of 5		NP_001193420.1
MAVS	NR_037921.2	n.414C>G		non_coding_transcript_exon_variant	Exon 3 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAVS	ENST00000428216.4	c.277C>G	p.Gln93Glu	missense_variant	Exon 3 of 7	1	NM_020746.5	ENSP00000401980.2
MAVS	ENST00000416600.6	c.-132+3053C>G		intron_variant	Intron 2 of 5	1		ENSP00000413749.2

Frequencies

GnomAD3 genomes AF: 0.230 AC: 34921 AN: 152074 Hom.: 4810 Cov.: 32

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.263

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.580

Gnomad SAS AF: 0.315

Gnomad FIN AF: 0.265

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.258

Gnomad OTH AF: 0.248

GnomAD3 exomes AF: 0.286 AC: 71842 AN: 251358 Hom.: 11651 AF XY: 0.290 AC XY: 39395 AN XY: 135860

Gnomad AFR exome AF: 0.0988

Gnomad AMR exome AF: 0.295

Gnomad ASJ exome AF: 0.252

Gnomad EAS exome AF: 0.574

Gnomad SAS exome AF: 0.330

Gnomad FIN exome AF: 0.267

Gnomad NFE exome AF: 0.259

Gnomad OTH exome AF: 0.263

GnomAD4 exome AF: 0.265 AC: 387488 AN: 1461802 Hom.: 54506 Cov.: 37 AF XY: 0.267 AC XY: 194468 AN XY: 727204

Gnomad4 AFR exome AF: 0.0955

Gnomad4 AMR exome AF: 0.293

Gnomad4 ASJ exome AF: 0.242

Gnomad4 EAS exome AF: 0.561

Gnomad4 SAS exome AF: 0.325

Gnomad4 FIN exome AF: 0.267

Gnomad4 NFE exome AF: 0.254

Gnomad4 OTH exome AF: 0.268

GnomAD4 genome AF: 0.229 AC: 34924 AN: 152192 Hom.: 4812 Cov.: 32 AF XY: 0.235 AC XY: 17469 AN XY: 74414

Gnomad4 AFR AF: 0.103

Gnomad4 AMR AF: 0.269

Gnomad4 ASJ AF: 0.247

Gnomad4 EAS AF: 0.580

Gnomad4 SAS AF: 0.313

Gnomad4 FIN AF: 0.265

Gnomad4 NFE AF: 0.258

Gnomad4 OTH AF: 0.245

Alfa AF: 0.247 Hom.: 3790

Bravo AF: 0.226

TwinsUK AF: 0.261 AC: 968

ALSPAC AF: 0.255 AC: 981

ESP6500AA AF: 0.103 AC: 452

ESP6500EA AF: 0.248 AC: 2136

ExAC AF: 0.280 AC: 34012

Asia WGS AF: 0.393 AC: 1366 AN: 3478

EpiCase AF: 0.254

EpiControl AF: 0.259

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	11
DANN	Benign	0.97
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.028	N
LIST_S2	Benign	0.72	T
MetaRNN	Benign	0.000062	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.2	L
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.51	N
REVEL	Benign	0.031
Sift	Benign	0.079	T
Sift4G	Uncertain	0.050	T
Polyphen		0.88	P
Vest4		0.069
MPC		0.18
ClinPred		0.010	T
GERP RS		2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.29
gMVP		0.11

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

Other links and lift over

dbSNP: rs17857295; hg19: chr20-3838441; COSMIC: COSV63926837;