chr20-3866196-C-T

Variant names:

• chr20-3866196-C-T
• rs3746660
• NM_020746.5:c.*49C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020746.5(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 NM_020746.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.683
• Publications: 17 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]

PANK2-AS1 (HGNC:40732): (PANK2 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MAVS	NM_020746.5	c.*49C>T		3_prime_UTR_variant	Exon 7 of 7	ENST00000428216.4	NP_065797.2
MAVS	NR_037921.2	n.1636C>T		non_coding_transcript_exon_variant	Exon 6 of 6
MAVS	NM_001206491.2	c.*49C>T		3_prime_UTR_variant	Exon 6 of 6		NP_001193420.1
MAVS	NM_001385663.1	c.*49C>T		3_prime_UTR_variant	Exon 8 of 8		NP_001372592.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAVS	ENST00000428216.4	c.*49C>T		3_prime_UTR_variant	Exon 7 of 7	1	NM_020746.5	ENSP00000401980.2
MAVS	ENST00000416600.6	c.*49C>T		3_prime_UTR_variant	Exon 6 of 6	1		ENSP00000413749.2
PANK2-AS1	ENST00000725518.1	n.426-3306G>A		intron_variant	Intron 1 of 1

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

GnomAD2 exomes AF: 0.407 AC: 61466 AN: 151072 AF XY: 0.415

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 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

African (AFR) AF: 0.156 AC: 4691 AN: 29982

American (AMR) AF: 0.428 AC: 13360 AN: 31250

Ashkenazi Jewish (ASJ) AF: 0.361 AC: 7392 AN: 20502

East Asian (EAS) AF: 0.238 AC: 9088 AN: 38248

South Asian (SAS) AF: 0.362 AC: 25947 AN: 71664

European-Finnish (FIN) AF: 0.468 AC: 16079 AN: 34376

Middle Eastern (MID) AF: 0.372 AC: 1968 AN: 5296

European-Non Finnish (NFE) AF: 0.472 AC: 492858 AN: 1043200

Other (OTH) AF: 0.416 AC: 23009 AN: 55356

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

African (AFR) AF: 0.167 AC: 6924 AN: 41538

American (AMR) AF: 0.401 AC: 6133 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.375 AC: 1300 AN: 3470

East Asian (EAS) AF: 0.224 AC: 1160 AN: 5170

South Asian (SAS) AF: 0.364 AC: 1754 AN: 4822

European-Finnish (FIN) AF: 0.481 AC: 5101 AN: 10606

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.458 AC: 31101 AN: 67952

Other (OTH) AF: 0.368 AC: 776 AN: 2108

Alfa AF: 0.431 Hom.: 15592

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
PhyloP100		-0.68
Mutation Taster		=100/0	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: rs3746660; hg19: chr20-3846843; COSMIC: COSV63926609;