20-3849020-G-A

Variant names:

• chr20-3849020-G-A
• rs6116065
• NM_020746.5:c.-68+2117G>A

Variant summary

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

The NM_020746.5(MAVS):​c.-68+2117G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 151,790 control chromosomes in the GnomAD database, including 10,106 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 0.36 (10106 hom., cov: 30)
• Consequence: MAVS NM_020746.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.411
• Publications: 11 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.655 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAVS	NM_020746.5	c.-68+2117G>A		intron_variant	Intron 1 of 6	ENST00000428216.4	NP_065797.2
MAVS	NM_001206491.2	c.-316+2117G>A		intron_variant	Intron 1 of 5		NP_001193420.1
MAVS	NM_001385663.1	c.-615+2117G>A		intron_variant	Intron 1 of 7		NP_001372592.1
MAVS	NR_037921.2	n.70+2117G>A		intron_variant	Intron 1 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAVS	ENST00000428216.4	c.-68+2117G>A		intron_variant	Intron 1 of 6	1	NM_020746.5	ENSP00000401980.2
MAVS	ENST00000416600.6	c.-316+2117G>A		intron_variant	Intron 1 of 5	1		ENSP00000413749.2

Frequencies

GnomAD3 genomes AF: 0.356 AC: 54058 AN: 151672 Hom.: 10087 Cov.: 30

Gnomad AFR AF: 0.353

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.369

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.674

Gnomad SAS AF: 0.476

Gnomad FIN AF: 0.406

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.375

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

GnomAD4 genome AF: 0.357 AC: 54119 AN: 151790 Hom.: 10106 Cov.: 30 AF XY: 0.364 AC XY: 26998 AN XY: 74172

African (AFR) AF: 0.354 AC: 14630 AN: 41382

American (AMR) AF: 0.370 AC: 5638 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.257 AC: 893 AN: 3470

East Asian (EAS) AF: 0.674 AC: 3473 AN: 5156

South Asian (SAS) AF: 0.476 AC: 2279 AN: 4788

European-Finnish (FIN) AF: 0.406 AC: 4273 AN: 10532

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.323 AC: 21936 AN: 67906

Other (OTH) AF: 0.375 AC: 789 AN: 2102

Alfa AF: 0.336 Hom.: 16519

Bravo AF: 0.356

Asia WGS AF: 0.560 AC: 1944 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.9
DANN	Benign	0.79
PhyloP100		0.41
Mutation Taster		=100/0	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: rs6116065; hg19: chr20-3829667;