rs3746660

Positions:

• chr20-3866196-C-T

Variant summary

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

The ENST00000428216.4(MAVS):​c.*49C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 1,482,026 control chromosomes in the GnomAD database, including 146,819 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 (11155 hom., cov: 32)
  • Exomes 𝑓: 0.45 (135664 hom.)
• Consequence: MAVS ENST00000428216.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.683

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAVS	NM_020746.5	c.*49C>T		3_prime_UTR_variant	7/7	ENST00000428216.4	NP_065797.2
MAVS	NM_001206491.2	c.*49C>T		3_prime_UTR_variant	6/6		NP_001193420.1
MAVS	NM_001385663.1	c.*49C>T		3_prime_UTR_variant	8/8		NP_001372592.1
MAVS	NR_037921.2	n.1636C>T		non_coding_transcript_exon_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAVS	ENST00000428216.4	c.*49C>T		3_prime_UTR_variant	7/7	1	NM_020746.5	ENSP00000401980	P1
MAVS	ENST00000416600.6	c.*49C>T		3_prime_UTR_variant	6/6	1		ENSP00000413749

Frequencies

GnomAD3 genomes AF: 0.361 AC: 54849 AN: 152034 Hom.: 11153 Cov.: 32

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.548

Gnomad AMR AF: 0.401

Gnomad ASJ AF: 0.375

Gnomad EAS AF: 0.226

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.481

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.458

Gnomad OTH AF: 0.370

GnomAD3 exomes AF: 0.407 AC: 61466 AN: 151072 Hom.: 12748 AF XY: 0.415 AC XY: 34214 AN XY: 82422

Gnomad AFR exome AF: 0.168

Gnomad AMR exome AF: 0.431

Gnomad ASJ exome AF: 0.368

Gnomad EAS exome AF: 0.236

Gnomad SAS exome AF: 0.376

Gnomad FIN exome AF: 0.480

Gnomad NFE exome AF: 0.475

Gnomad OTH exome AF: 0.434

GnomAD4 exome AF: 0.447 AC: 594392 AN: 1329874 Hom.: 135664 Cov.: 23 AF XY: 0.445 AC XY: 290867 AN XY: 653254

Gnomad4 AFR exome AF: 0.156

Gnomad4 AMR exome AF: 0.428

Gnomad4 ASJ exome AF: 0.361

Gnomad4 EAS exome AF: 0.238

Gnomad4 SAS exome AF: 0.362

Gnomad4 FIN exome AF: 0.468

Gnomad4 NFE exome AF: 0.472

Gnomad4 OTH exome AF: 0.416

GnomAD4 genome AF: 0.361 AC: 54861 AN: 152152 Hom.: 11155 Cov.: 32 AF XY: 0.361 AC XY: 26845 AN XY: 74386

Gnomad4 AFR AF: 0.167

Gnomad4 AMR AF: 0.401

Gnomad4 ASJ AF: 0.375

Gnomad4 EAS AF: 0.224

Gnomad4 SAS AF: 0.364

Gnomad4 FIN AF: 0.481

Gnomad4 NFE AF: 0.458

Gnomad4 OTH AF: 0.368

Alfa AF: 0.432 Hom.: 13308

Bravo AF: 0.350

Asia WGS AF: 0.308 AC: 1069 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.60
DANN	Benign	0.46

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: rs3746660; hg19: chr20-3846843; COSMIC: COSV63926609;