rs45437096

Variant names:

• chr20-3864282-C-G
• rs45437096
• NM_020746.5:c.652C>G
• MAVS p.Arg218Gly

Your query was ambiguous. Multiple possible variants found:

• chr20-3864282-C-G
• chr20-3864282-C-T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_020746.5(MAVS):​c.652C>G​(p.Arg218Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000891 in 1,459,542 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as (no stars). 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000089 (0 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.15251487).
• BS2: High AC in GnomAdExome4 at 13 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020746.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAVS	NM_020746.5	MANE Select	c.652C>G	p.Arg218Gly	missense	Exon 6 of 7	NP_065797.2	Q7Z434-1
	MAVS	NM_001206491.2		c.229C>G	p.Arg77Gly	missense	Exon 5 of 6	NP_001193420.1	Q7Z434-4
	MAVS	NM_001385663.1		c.229C>G	p.Arg77Gly	missense	Exon 7 of 8	NP_001372592.1	Q7Z434-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAVS	ENST00000428216.4	TSL:1 MANE Select	c.652C>G	p.Arg218Gly	missense	Exon 6 of 7	ENSP00000401980.2	Q7Z434-1
	MAVS	ENST00000416600.6	TSL:1	c.229C>G	p.Arg77Gly	missense	Exon 5 of 6	ENSP00000413749.2	Q7Z434-4
	MAVS	ENST00000883971.1		c.652C>G	p.Arg218Gly	missense	Exon 5 of 6	ENSP00000554030.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000804 AC: 2 AN: 248682 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000178

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000891 AC: 13 AN: 1459542 Hom.: 0 Cov.: 33 AF XY: 0.0000138 AC XY: 10 AN XY: 725900

African (AFR) AF: 0.00 AC: 0 AN: 33444

American (AMR) AF: 0.00 AC: 0 AN: 44416

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25874

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86058

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53294

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 0.00000990 AC: 11 AN: 1110742

Other (OTH) AF: 0.0000332 AC: 2 AN: 60278

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 3582

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	10
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.052	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.0094	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		-0.93
PrimateAI	Benign	0.25	T
PROVEAN	Pathogenic	-5.2	D
REVEL	Benign	0.068
Sift	Benign	0.14	T
Sift4G	Benign	0.44	T
Varity_R		0.12
gMVP		0.22
Mutation Taster		=80/20	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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.

Other links and lift over

dbSNP: rs45437096;

hg19: chr20-3844929;