rs7262903

Variant names:

• chr20-3862380-C-A
• rs7262903
• NM_020746.5:c.592C>A

Your query was ambiguous. Multiple possible variants found:

• chr20-3862380-C-A
• chr20-3862380-C-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.592C>A​(p.Gln198Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 1,613,710 control chromosomes in the GnomAD database, including 19,824 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.16 (1973 hom., cov: 33)
  • Exomes 𝑓: 0.15 (17851 hom.)
• Consequence: MAVS NM_020746.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.223
• Publications: 52 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=0.001180917).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAVS	NM_020746.5	c.592C>A	p.Gln198Lys	missense_variant	Exon 5 of 7	ENST00000428216.4	NP_065797.2
MAVS	NM_001206491.2	c.169C>A	p.Gln57Lys	missense_variant	Exon 4 of 6		NP_001193420.1
MAVS	NM_001385663.1	c.169C>A	p.Gln57Lys	missense_variant	Exon 6 of 8		NP_001372592.1
MAVS	NR_037921.2	n.556C>A		non_coding_transcript_exon_variant	Exon 4 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAVS	ENST00000428216.4	c.592C>A	p.Gln198Lys	missense_variant	Exon 5 of 7	1	NM_020746.5	ENSP00000401980.2
MAVS	ENST00000416600.6	c.169C>A	p.Gln57Lys	missense_variant	Exon 4 of 6	1		ENSP00000413749.2
PANK2-AS1	ENST00000725518.1	n.*233G>T		downstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.158 AC: 24048 AN: 152038 Hom.: 1973 Cov.: 33

Gnomad AFR AF: 0.189

Gnomad AMI AF: 0.0815

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.0890

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.166

GnomAD2 exomes AF: 0.145 AC: 36292 AN: 251024 AF XY: 0.148

Gnomad AFR exome AF: 0.189

Gnomad AMR exome AF: 0.0932

Gnomad ASJ exome AF: 0.178

Gnomad EAS exome AF: 0.103

Gnomad FIN exome AF: 0.113

Gnomad NFE exome AF: 0.154

Gnomad OTH exome AF: 0.159

GnomAD4 exome AF: 0.153 AC: 223649 AN: 1461554 Hom.: 17851 Cov.: 32 AF XY: 0.154 AC XY: 112273 AN XY: 727088

African (AFR) AF: 0.191 AC: 6410 AN: 33476

American (AMR) AF: 0.0975 AC: 4358 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 4379 AN: 26132

East Asian (EAS) AF: 0.111 AC: 4409 AN: 39692

South Asian (SAS) AF: 0.177 AC: 15266 AN: 86234

European-Finnish (FIN) AF: 0.114 AC: 6106 AN: 53354

Middle Eastern (MID) AF: 0.202 AC: 1167 AN: 5768

European-Non Finnish (NFE) AF: 0.155 AC: 172109 AN: 1111810

Other (OTH) AF: 0.156 AC: 9445 AN: 60372

GnomAD4 genome AF: 0.158 AC: 24060 AN: 152156 Hom.: 1973 Cov.: 33 AF XY: 0.155 AC XY: 11568 AN XY: 74394

African (AFR) AF: 0.189 AC: 7832 AN: 41504

American (AMR) AF: 0.136 AC: 2071 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 547 AN: 3472

East Asian (EAS) AF: 0.0890 AC: 460 AN: 5168

South Asian (SAS) AF: 0.179 AC: 866 AN: 4826

European-Finnish (FIN) AF: 0.108 AC: 1149 AN: 10594

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.157 AC: 10650 AN: 68002

Other (OTH) AF: 0.165 AC: 348 AN: 2112

Alfa AF: 0.156 Hom.: 6501

Bravo AF: 0.160

TwinsUK AF: 0.162 AC: 599

ALSPAC AF: 0.137 AC: 529

ESP6500AA AF: 0.187 AC: 825

ESP6500EA AF: 0.162 AC: 1396

ExAC AF: 0.148 AC: 17984

Asia WGS AF: 0.127 AC: 445 AN: 3478

EpiCase AF: 0.163

EpiControl AF: 0.160

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.17	.;T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.36
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.68	T;T
MetaRNN	Benign	0.0012	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	.;M
PhyloP100		0.22
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-3.5	D;N
REVEL	Benign	0.064
Sift	Benign	0.055	T;D
Sift4G	Benign	0.19	T;T
Polyphen		0.98	.;D
Vest4		0.24
MPC		0.32
ClinPred		0.034	T
GERP RS		1.1
Varity_R		0.11
gMVP		0.21
Mutation Taster		=86/14	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: rs7262903; hg19: chr20-3843027; COSMIC: COSV63926592;