chr20-3864282-C-T

Variant names:

• chr20-3864282-C-T
• rs45437096
• NM_020746.5:c.652C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020746.5(MAVS):​c.652C>T​(p.Arg218Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 1,611,608 control chromosomes in the GnomAD database, including 16,102 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. R218H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.11 (1105 hom., cov: 32)
  • Exomes 𝑓: 0.14 (14997 hom.)
• Consequence: MAVS NM_020746.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.931
• Publications: 17 publications found

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]

PANK2-AS1 (HGNC:40732): (PANK2 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.0014338195).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAVS	NM_020746.5	c.652C>T	p.Arg218Cys	missense_variant	Exon 6 of 7	ENST00000428216.4	NP_065797.2
MAVS	NM_001206491.2	c.229C>T	p.Arg77Cys	missense_variant	Exon 5 of 6		NP_001193420.1
MAVS	NM_001385663.1	c.229C>T	p.Arg77Cys	missense_variant	Exon 7 of 8		NP_001372592.1
MAVS	NR_037921.2	n.616C>T		non_coding_transcript_exon_variant	Exon 5 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAVS	ENST00000428216.4	c.652C>T	p.Arg218Cys	missense_variant	Exon 6 of 7	1	NM_020746.5	ENSP00000401980.2
MAVS	ENST00000416600.6	c.229C>T	p.Arg77Cys	missense_variant	Exon 5 of 6	1		ENSP00000413749.2
PANK2-AS1	ENST00000725518.1	n.426-1392G>A		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.105 AC: 16001 AN: 152048 Hom.: 1105 Cov.: 32

Gnomad AFR AF: 0.0285

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.0344

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.127

GnomAD2 exomes AF: 0.109 AC: 27058 AN: 248682 AF XY: 0.110

Gnomad AFR exome AF: 0.0264

Gnomad AMR exome AF: 0.0785

Gnomad ASJ exome AF: 0.142

Gnomad EAS exome AF: 0.00131

Gnomad FIN exome AF: 0.112

Gnomad NFE exome AF: 0.162

Gnomad OTH exome AF: 0.144

GnomAD4 exome AF: 0.136 AC: 198980 AN: 1459442 Hom.: 14997 Cov.: 33 AF XY: 0.135 AC XY: 97700 AN XY: 725846

African (AFR) AF: 0.0251 AC: 839 AN: 33442

American (AMR) AF: 0.0830 AC: 3685 AN: 44412

Ashkenazi Jewish (ASJ) AF: 0.142 AC: 3683 AN: 25866

East Asian (EAS) AF: 0.00103 AC: 41 AN: 39686

South Asian (SAS) AF: 0.0371 AC: 3197 AN: 86058

European-Finnish (FIN) AF: 0.112 AC: 5977 AN: 53284

Middle Eastern (MID) AF: 0.140 AC: 807 AN: 5746

European-Non Finnish (NFE) AF: 0.156 AC: 173104 AN: 1110672

Other (OTH) AF: 0.127 AC: 7647 AN: 60276

GnomAD4 genome AF: 0.105 AC: 15996 AN: 152166 Hom.: 1105 Cov.: 32 AF XY: 0.102 AC XY: 7551 AN XY: 74394

African (AFR) AF: 0.0284 AC: 1178 AN: 41520

American (AMR) AF: 0.110 AC: 1684 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 521 AN: 3468

East Asian (EAS) AF: 0.00193 AC: 10 AN: 5180

South Asian (SAS) AF: 0.0346 AC: 167 AN: 4824

European-Finnish (FIN) AF: 0.108 AC: 1143 AN: 10606

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.159 AC: 10819 AN: 67962

Other (OTH) AF: 0.125 AC: 265 AN: 2114

Alfa AF: 0.139 Hom.: 3582

Bravo AF: 0.103

TwinsUK AF: 0.138 AC: 513

ALSPAC AF: 0.144 AC: 556

ESP6500AA AF: 0.0384 AC: 169

ESP6500EA AF: 0.165 AC: 1418

ExAC AF: 0.110 AC: 13311

Asia WGS AF: 0.0180 AC: 64 AN: 3478

EpiCase AF: 0.168

EpiControl AF: 0.167

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	14
DANN	Benign	0.97
DEOGEN2	Benign	0.17	.;T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.82	T;T
MetaRNN	Benign	0.0014	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.0	.;M
PhyloP100		-0.93
PrimateAI	Benign	0.26	T
PROVEAN	Pathogenic	-5.1	D;D
REVEL	Benign	0.035
Sift	Benign	0.14	T;T
Sift4G	Benign	0.20	T;T
Polyphen		0.015	.;B
Vest4		0.17
MPC		0.19
ClinPred		0.041	T
GERP RS		0.35
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.085
gMVP		0.20
Mutation Taster		=79/21	polymorphism (auto)

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

Other links and lift over

dbSNP: rs45437096; hg19: chr20-3844929; COSMIC: COSV63927889;