rs2326369

Variant names:

• chr20-3862337-C-T
• rs2326369
• NM_020746.5:c.549C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_020746.5(MAVS):​c.549C>T​(p.Asp183Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0707 in 1,613,834 control chromosomes in the GnomAD database, including 5,618 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 0.11 (1145 hom., cov: 33)
  • Exomes 𝑓: 0.067 (4473 hom.)
• Consequence: MAVS NM_020746.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.575
• Publications: 21 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP7: Synonymous conserved (PhyloP=0.575 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.217 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAVS	NM_020746.5	c.549C>T	p.Asp183Asp	synonymous_variant	Exon 5 of 7	ENST00000428216.4	NP_065797.2
MAVS	NM_001206491.2	c.126C>T	p.Asp42Asp	synonymous_variant	Exon 4 of 6		NP_001193420.1
MAVS	NM_001385663.1	c.126C>T	p.Asp42Asp	synonymous_variant	Exon 6 of 8		NP_001372592.1
MAVS	NR_037921.2	n.513C>T		non_coding_transcript_exon_variant	Exon 4 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAVS	ENST00000428216.4	c.549C>T	p.Asp183Asp	synonymous_variant	Exon 5 of 7	1	NM_020746.5	ENSP00000401980.2
MAVS	ENST00000416600.6	c.126C>T	p.Asp42Asp	synonymous_variant	Exon 4 of 6	1		ENSP00000413749.2

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16099 AN: 152120 Hom.: 1140 Cov.: 33

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.0581

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.0839

Gnomad EAS AF: 0.226

Gnomad SAS AF: 0.0913

Gnomad FIN AF: 0.0646

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0530

Gnomad OTH AF: 0.113

GnomAD2 exomes AF: 0.0915 AC: 22981 AN: 251026 AF XY: 0.0863

Gnomad AFR exome AF: 0.198

Gnomad AMR exome AF: 0.111

Gnomad ASJ exome AF: 0.0782

Gnomad EAS exome AF: 0.230

Gnomad FIN exome AF: 0.0653

Gnomad NFE exome AF: 0.0570

Gnomad OTH exome AF: 0.0783

GnomAD4 exome AF: 0.0671 AC: 98008 AN: 1461596 Hom.: 4473 Cov.: 31 AF XY: 0.0671 AC XY: 48755 AN XY: 727070

African (AFR) AF: 0.203 AC: 6804 AN: 33454

American (AMR) AF: 0.110 AC: 4931 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.0794 AC: 2075 AN: 26136

East Asian (EAS) AF: 0.231 AC: 9143 AN: 39666

South Asian (SAS) AF: 0.0862 AC: 7431 AN: 86220

European-Finnish (FIN) AF: 0.0655 AC: 3494 AN: 53348

Middle Eastern (MID) AF: 0.105 AC: 608 AN: 5768

European-Non Finnish (NFE) AF: 0.0528 AC: 58667 AN: 1111924

Other (OTH) AF: 0.0804 AC: 4855 AN: 60388

GnomAD4 genome AF: 0.106 AC: 16135 AN: 152238 Hom.: 1145 Cov.: 33 AF XY: 0.107 AC XY: 7988 AN XY: 74414

African (AFR) AF: 0.194 AC: 8059 AN: 41528

American (AMR) AF: 0.102 AC: 1555 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0839 AC: 291 AN: 3470

East Asian (EAS) AF: 0.227 AC: 1176 AN: 5172

South Asian (SAS) AF: 0.0918 AC: 443 AN: 4826

European-Finnish (FIN) AF: 0.0646 AC: 686 AN: 10614

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0530 AC: 3606 AN: 68020

Other (OTH) AF: 0.113 AC: 240 AN: 2116

Alfa AF: 0.0742 Hom.: 943

Bravo AF: 0.113

Asia WGS AF: 0.156 AC: 541 AN: 3478

EpiCase AF: 0.0570

EpiControl AF: 0.0579

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	5.6
DANN	Benign	0.55
PhyloP100		0.57
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: rs2326369; hg19: chr20-3842984; COSMIC: COSV63926961;