20-3857753-G-T

Variant names:

• chr20-3857753-G-T
• rs11905552
• NM_020746.5:c.236G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 28 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 (MetaRNN=0.0034611523).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001385663.1. 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.236G>T	p.Cys79Phe	missense	Exon 3 of 7	NP_065797.2	Q7Z434-1
	MAVS	NM_001385663.1		c.-312G>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 8	NP_001372592.1	Q7Z434-4
	MAVS	NM_001385663.1		c.-312G>T		5_prime_UTR	Exon 3 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.236G>T	p.Cys79Phe	missense	Exon 3 of 7	ENSP00000401980.2	Q7Z434-1
	MAVS	ENST00000416600.6	TSL:1	c.-132+3012G>T		intron	N/A	ENSP00000413749.2	Q7Z434-4
	MAVS	ENST00000883971.1		c.236G>T	p.Cys79Phe	missense	Exon 2 of 6	ENSP00000554030.1

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

GnomAD2 exomes AF: 0.00971 AC: 2442 AN: 251478 AF XY: 0.00686

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 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

African (AFR) AF: 0.133 AC: 4445 AN: 33478

American (AMR) AF: 0.00789 AC: 353 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000243 AC: 21 AN: 86258

European-Finnish (FIN) AF: 0.000693 AC: 37 AN: 53418

Middle Eastern (MID) AF: 0.00607 AC: 35 AN: 5768

European-Non Finnish (NFE) AF: 0.000248 AC: 276 AN: 1112008

Other (OTH) AF: 0.00856 AC: 517 AN: 60396

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

African (AFR) AF: 0.126 AC: 5226 AN: 41540

American (AMR) AF: 0.0135 AC: 206 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.000376 AC: 4 AN: 10626

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.000500 AC: 34 AN: 68036

Other (OTH) AF: 0.0350 AC: 74 AN: 2114

Alfa AF: 0.0138 Hom.: 292

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 v4.9

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
PhyloP100		4.3
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
Mutation Taster		=93/7	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: rs11905552; hg19: chr20-3838400; COSMIC: COSV63926840;