20-3846618-G-C

Variant names:

• chr20-3846618-G-C
• rs3899452
• NM_020746.5:c.-353G>C

Variant summary

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

The NM_020746.5(MAVS):​c.-353G>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 152,072 control chromosomes in the GnomAD database, including 3,346 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 0.19 (3346 hom., cov: 32)
• Consequence: MAVS NM_020746.5 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03
• Publications: 5 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAVS	NM_020746.5	c.-353G>C		upstream_gene_variant		ENST00000428216.4	NP_065797.2
MAVS	NM_001206491.2	c.-601G>C		upstream_gene_variant			NP_001193420.1
MAVS	NM_001385663.1	c.-900G>C		upstream_gene_variant			NP_001372592.1
MAVS	NR_037921.2	n.-216G>C		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAVS	ENST00000428216.4	c.-353G>C		upstream_gene_variant		1	NM_020746.5	ENSP00000401980.2
MAVS	ENST00000416600.6	c.-601G>C		upstream_gene_variant		1		ENSP00000413749.2

Frequencies

GnomAD3 genomes AF: 0.191 AC: 29057 AN: 151954 Hom.: 3347 Cov.: 32

Gnomad AFR AF: 0.314

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.292

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.165

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.191 AC: 29084 AN: 152072 Hom.: 3346 Cov.: 32 AF XY: 0.191 AC XY: 14208 AN XY: 74340

African (AFR) AF: 0.313 AC: 12991 AN: 41450

American (AMR) AF: 0.152 AC: 2323 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.176 AC: 610 AN: 3470

East Asian (EAS) AF: 0.292 AC: 1509 AN: 5160

South Asian (SAS) AF: 0.150 AC: 724 AN: 4816

European-Finnish (FIN) AF: 0.170 AC: 1797 AN: 10598

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.127 AC: 8619 AN: 67980

Other (OTH) AF: 0.164 AC: 345 AN: 2102

Alfa AF: 0.0698 Hom.: 87

Bravo AF: 0.197

Asia WGS AF: 0.206 AC: 717 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.0
DANN	Benign	0.63
PhyloP100		-1.0
PromoterAI		0.024	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3899452; hg19: chr20-3827265;