20-3857753-G-T

Position:

• chr20-3857753-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001385663.1(MAVS):​c.-312G>T variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.00696 in 1,614,194 control chromosomes in the GnomAD database, including 630 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 0.036 (325 hom., cov: 33)
  • Exomes 𝑓: 0.0039 (305 hom.)
• Consequence: MAVS NM_001385663.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.26

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]

MAVS (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0034611523).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAVS	NM_020746.5	c.236G>T	p.Cys79Phe	missense_variant	3/7	ENST00000428216.4	NP_065797.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAVS	ENST00000428216.4	c.236G>T	p.Cys79Phe	missense_variant	3/7	1	NM_020746.5	ENSP00000401980.2
MAVS	ENST00000416600.6	c.-132+3012G>T		intron_variant		1		ENSP00000413749.2

Frequencies

GnomAD3 genomes AF: 0.0364 AC: 5544 AN: 152190 Hom.: 324 Cov.: 33

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0135

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000376

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000500

Gnomad OTH AF: 0.0354

GnomAD3 exomes AF: 0.00971 AC: 2442 AN: 251478 Hom.: 143 AF XY: 0.00686 AC XY: 932 AN XY: 135916

Gnomad AFR exome AF: 0.128

Gnomad AMR exome AF: 0.00700

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000980

Gnomad FIN exome AF: 0.000785

Gnomad NFE exome AF: 0.000527

Gnomad OTH exome AF: 0.00537

GnomAD4 exome AF: 0.00389 AC: 5685 AN: 1461886 Hom.: 305 Cov.: 32 AF XY: 0.00339 AC XY: 2463 AN XY: 727240

Gnomad4 AFR exome AF: 0.133

Gnomad4 AMR exome AF: 0.00789

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000243

Gnomad4 FIN exome AF: 0.000693

Gnomad4 NFE exome AF: 0.000248

Gnomad4 OTH exome AF: 0.00856

GnomAD4 genome AF: 0.0364 AC: 5549 AN: 152308 Hom.: 325 Cov.: 33 AF XY: 0.0346 AC XY: 2574 AN XY: 74480

Gnomad4 AFR AF: 0.126

Gnomad4 AMR AF: 0.0135

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.000376

Gnomad4 NFE AF: 0.000500

Gnomad4 OTH AF: 0.0350

Alfa AF: 0.00657 Hom.: 85

Bravo AF: 0.0423

ESP6500AA AF: 0.00363 AC: 16

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0115 AC: 1400

Asia WGS AF: 0.00491 AC: 17 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000652

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.82
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Uncertain	0.020
CADD	Benign	23
DANN	Benign	0.96
DEOGEN2	Benign	0.27	T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.76	T
MetaRNN	Benign	0.0035	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	1.1	L
PrimateAI	Benign	0.47	T
PROVEAN	Pathogenic	-7.4	D
REVEL	Uncertain	0.29
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.17	T
Polyphen		1.0	D
Vest4		0.36
MPC		0.24
ClinPred		0.084	T
GERP RS		4.7
Varity_R		0.88
gMVP		0.54

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

Publications

LitVar

Other links and lift over

dbSNP: rs11905552; hg19: chr20-3838400; COSMIC: COSV63926840;