20-3865761-G-A

Position:

• chr20-3865761-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_020746.5(MAVS):​c.1237G>A​(p.Gly413Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00159 in 1,613,660 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0084 (16 hom., cov: 33)
  • Exomes 𝑓: 0.00088 (16 hom.)
• Consequence: MAVS NM_020746.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0490

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0034693182).
• BP6: Variant 20-3865761-G-A is Benign according to our data. Variant chr20-3865761-G-A is described in ClinVar as [Benign]. Clinvar id is 769074.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00844 (1286/152308) while in subpopulation AFR AF= 0.0298 (1239/41572). AF 95% confidence interval is 0.0284. There are 16 homozygotes in gnomad4. There are 613 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1286 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAVS	NM_020746.5	c.1237G>A	p.Gly413Ser	missense_variant	7/7	ENST00000428216.4
MAVS	NM_001206491.2	c.814G>A	p.Gly272Ser	missense_variant	6/6
MAVS	NM_001385663.1	c.814G>A	p.Gly272Ser	missense_variant	8/8
MAVS	NR_037921.2	n.1201G>A		non_coding_transcript_exon_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAVS	ENST00000428216.4	c.1237G>A	p.Gly413Ser	missense_variant	7/7	1	NM_020746.5	P1
MAVS	ENST00000416600.6	c.814G>A	p.Gly272Ser	missense_variant	6/6	1

Frequencies

GnomAD3 genomes AF: 0.00837 AC: 1274 AN: 152190 Hom.: 14 Cov.: 33

Gnomad AFR AF: 0.0296

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00229

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00478

GnomAD3 exomes AF: 0.00228 AC: 570 AN: 250524 Hom.: 4 AF XY: 0.00159 AC XY: 216 AN XY: 135690

Gnomad AFR exome AF: 0.0313

Gnomad AMR exome AF: 0.00136

Gnomad ASJ exome AF: 0.000199

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000980

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000619

Gnomad OTH exome AF: 0.000818

GnomAD4 exome AF: 0.000878 AC: 1283 AN: 1461352 Hom.: 16 Cov.: 32 AF XY: 0.000763 AC XY: 555 AN XY: 726988

Gnomad4 AFR exome AF: 0.0298

Gnomad4 AMR exome AF: 0.00183

Gnomad4 ASJ exome AF: 0.000344

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000209

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000153

Gnomad4 OTH exome AF: 0.00245

GnomAD4 genome AF: 0.00844 AC: 1286 AN: 152308 Hom.: 16 Cov.: 33 AF XY: 0.00823 AC XY: 613 AN XY: 74478

Gnomad4 AFR AF: 0.0298

Gnomad4 AMR AF: 0.00216

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.00168 Hom.: 5

Bravo AF: 0.00941

ESP6500AA AF: 0.0284 AC: 125

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00276 AC: 335

Asia WGS AF: 0.00346 AC: 12 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 06, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	3.2
DANN	Benign	0.65
DEOGEN2	Benign	0.059	.;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.053	N
LIST_S2	Benign	0.47	T;T
MetaRNN	Benign	0.0035	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	.;L
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.9	N;N
REVEL	Benign	0.037
Sift	Benign	0.34	T;T
Sift4G	Benign	0.76	T;T
Polyphen		0.12	.;B
Vest4		0.041
MVP		0.41
MPC		0.13
ClinPred		0.0036	T
GERP RS		-0.43
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.022
gMVP		0.075

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: rs62640879; hg19: chr20-3846408;