rs2464

Positions:

• chr20-3874335-C-T

Variant summary

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

The NM_020746.5(MAVS):​c.*8188C>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 0.398 in 397,218 control chromosomes in the GnomAD database, including 33,943 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 (11172 hom., cov: 31)
  • Exomes 𝑓: 0.42 (22771 hom.)
• Consequence: MAVS NM_020746.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0390

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 (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAVS	NM_020746.5	c.*8188C>T		3_prime_UTR_variant	7/7	ENST00000428216.4	NP_065797.2
MAVS	NM_001206491.2	c.*8188C>T		3_prime_UTR_variant	6/6		NP_001193420.1
MAVS	NM_001385663.1	c.*8188C>T		3_prime_UTR_variant	8/8		NP_001372592.1
MAVS	NR_037921.2	n.9775C>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.*8188C>T		3_prime_UTR_variant	7/7	1	NM_020746.5	ENSP00000401980.2
MAVS	ENST00000416600.6	c.*8188C>T		3_prime_UTR_variant	6/6	1		ENSP00000413749.2

Frequencies

GnomAD3 genomes AF: 0.360 AC: 54690 AN: 151734 Hom.: 11169 Cov.: 31

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.547

Gnomad AMR AF: 0.405

Gnomad ASJ AF: 0.374

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.389

Gnomad FIN AF: 0.480

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.460

Gnomad OTH AF: 0.370

GnomAD4 exome AF: 0.421 AC: 103420 AN: 245366 Hom.: 22771 Cov.: 0 AF XY: 0.423 AC XY: 52637 AN XY: 124346

Gnomad4 AFR exome AF: 0.165

Gnomad4 AMR exome AF: 0.422

Gnomad4 ASJ exome AF: 0.362

Gnomad4 EAS exome AF: 0.225

Gnomad4 SAS exome AF: 0.367

Gnomad4 FIN exome AF: 0.465

Gnomad4 NFE exome AF: 0.463

Gnomad4 OTH exome AF: 0.397

GnomAD4 genome AF: 0.360 AC: 54698 AN: 151852 Hom.: 11172 Cov.: 31 AF XY: 0.361 AC XY: 26782 AN XY: 74190

Gnomad4 AFR AF: 0.159

Gnomad4 AMR AF: 0.406

Gnomad4 ASJ AF: 0.374

Gnomad4 EAS AF: 0.215

Gnomad4 SAS AF: 0.390

Gnomad4 FIN AF: 0.480

Gnomad4 NFE AF: 0.460

Gnomad4 OTH AF: 0.369

Alfa AF: 0.383 Hom.: 2357

Bravo AF: 0.348

Asia WGS AF: 0.316 AC: 1099 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.63
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs2464; hg19: chr20-3854982;