rs6515831

chr20-3871304-T-C

Variant summary

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

The NM_020746.5(MAVS):c.*5157T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.362 in 153,774 control chromosomes in the GnomAD database, including 11,452 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 (11275 hom., cov: 32)
  • Exomes 𝑓: 0.46 (177 hom.)
• Consequence: MAVS NM_020746.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.882

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=-0.68).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAVS	NM_020746.5	c.*5157T>C		3_prime_UTR_variant	7/7	ENST00000428216.4
MAVS	NM_001206491.2	c.*5157T>C		3_prime_UTR_variant	6/6
MAVS	NM_001385663.1	c.*5157T>C		3_prime_UTR_variant	8/8
MAVS	NR_037921.2	n.6744T>C		non_coding_transcript_exon_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAVS	ENST00000428216.4	c.*5157T>C		3_prime_UTR_variant	7/7	1	NM_020746.5	P1
MAVS	ENST00000416600.6	c.*5157T>C		3_prime_UTR_variant	6/6	1

Frequencies

GnomAD3 genomes AF: 0.361 AC: 54913 AN: 151958 Hom.: 11271 Cov.: 32

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.546

Gnomad AMR AF: 0.406

Gnomad ASJ AF: 0.375

Gnomad EAS AF: 0.225

Gnomad SAS AF: 0.395

Gnomad FIN AF: 0.477

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.460

Gnomad OTH AF: 0.374

GnomAD4 exome AF: 0.463 AC: 786 AN: 1698 Hom.: 177 Cov.: 0 AF XY: 0.431 AC XY: 383 AN XY: 888

Gnomad4 AFR exome AF: 0.500

Gnomad4 EAS exome AF: 0.423

Gnomad4 FIN exome AF: 0.465

Gnomad4 NFE exome AF: 0.545

Gnomad4 OTH exome AF: 0.438

GnomAD4 genome AF: 0.361 AC: 54922 AN: 152076 Hom.: 11275 Cov.: 32 AF XY: 0.362 AC XY: 26883 AN XY: 74324

Gnomad4 AFR AF: 0.160

Gnomad4 AMR AF: 0.407

Gnomad4 ASJ AF: 0.375

Gnomad4 EAS AF: 0.224

Gnomad4 SAS AF: 0.396

Gnomad4 FIN AF: 0.477

Gnomad4 NFE AF: 0.460

Gnomad4 OTH AF: 0.373

Alfa AF: 0.438 Hom.: 15148

Bravo AF: 0.350

Asia WGS AF: 0.326 AC: 1131 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
Cadd	Benign	8.1
Dann	Benign	0.91

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs6515831; hg19: chr20-3851951; COSMIC: COSV70425506;