rs62640879

Variant names:

• chr20-3865761-G-A
• rs62640879
• NM_020746.5:c.1237G>A

Variant summary

Our verdict is Benign. The variant received -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. 15/21 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
• Publications: 3 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 -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1286 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020746.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAVS	NM_020746.5	MANE Select	c.1237G>A	p.Gly413Ser	missense	Exon 7 of 7	NP_065797.2	Q7Z434-1
	MAVS	NM_001206491.2		c.814G>A	p.Gly272Ser	missense	Exon 6 of 6	NP_001193420.1	Q7Z434-4
	MAVS	NM_001385663.1		c.814G>A	p.Gly272Ser	missense	Exon 8 of 8	NP_001372592.1	Q7Z434-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAVS	ENST00000428216.4	TSL:1 MANE Select	c.1237G>A	p.Gly413Ser	missense	Exon 7 of 7	ENSP00000401980.2	Q7Z434-1
	MAVS	ENST00000416600.6	TSL:1	c.814G>A	p.Gly272Ser	missense	Exon 6 of 6	ENSP00000413749.2	Q7Z434-4
	MAVS	ENST00000883971.1		c.1267G>A	p.Gly423Ser	missense	Exon 6 of 6	ENSP00000554030.1

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

GnomAD2 exomes AF: 0.00228 AC: 570 AN: 250524 AF XY: 0.00159

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 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

African (AFR) AF: 0.0298 AC: 999 AN: 33474

American (AMR) AF: 0.00183 AC: 82 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.000344 AC: 9 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000209 AC: 18 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52956

Middle Eastern (MID) AF: 0.00174 AC: 10 AN: 5746

European-Non Finnish (NFE) AF: 0.0000153 AC: 17 AN: 1111982

Other (OTH) AF: 0.00245 AC: 148 AN: 60380

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

African (AFR) AF: 0.0298 AC: 1239 AN: 41572

American (AMR) AF: 0.00216 AC: 33 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68022

Other (OTH) AF: 0.00473 AC: 10 AN: 2114

Alfa AF: 0.00186 Hom.: 6

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

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

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
MetaRNN	Benign	0.0035	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L
PhyloP100		0.049
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.037
Sift	Benign	0.34	T
Sift4G	Benign	0.76	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
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs62640879; hg19: chr20-3846408;