rs114219049

Variant names:

• chr20-3857815-C-T
• rs114219049
• NM_020746.5:c.292+6C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_020746.5(MAVS):​c.292+6C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00328 in 1,614,098 control chromosomes in the GnomAD database, including 133 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (58 hom., cov: 32)
  • Exomes 𝑓: 0.0019 (75 hom.)
• Consequence: MAVS NM_020746.5 splice_region, intron
• Scores: Splicing: ADA: 0.00003243
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.382
• Publications: 2 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 20-3857815-C-T is Benign according to our data. Variant chr20-3857815-C-T is described in ClinVar as Benign. ClinVar VariationId is 780585.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0528 is higher than 0.05.

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.292+6C>T		splice_region intron	N/A	NP_065797.2	Q7Z434-1
	MAVS	NM_001206491.2		c.-132+3074C>T		intron	N/A	NP_001193420.1	Q7Z434-4
	MAVS	NM_001385663.1		c.-256+6C>T		splice_region intron	N/A	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.292+6C>T		splice_region intron	N/A	ENSP00000401980.2	Q7Z434-1
	MAVS	ENST00000416600.6	TSL:1	c.-132+3074C>T		intron	N/A	ENSP00000413749.2	Q7Z434-4
	MAVS	ENST00000883971.1		c.292+6C>T		splice_region intron	N/A	ENSP00000554030.1

Frequencies

GnomAD3 genomes AF: 0.0161 AC: 2449 AN: 152194 Hom.: 58 Cov.: 32

Gnomad AFR AF: 0.0548

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00707

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000367

Gnomad OTH AF: 0.0177

GnomAD2 exomes AF: 0.00471 AC: 1184 AN: 251308 AF XY: 0.00337

Gnomad AFR exome AF: 0.0570

Gnomad AMR exome AF: 0.00477

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.000788

Gnomad NFE exome AF: 0.000431

Gnomad OTH exome AF: 0.00326

GnomAD4 exome AF: 0.00194 AC: 2843 AN: 1461786 Hom.: 75 Cov.: 33 AF XY: 0.00173 AC XY: 1260 AN XY: 727198

African (AFR) AF: 0.0598 AC: 2003 AN: 33478

American (AMR) AF: 0.00510 AC: 228 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.000174 AC: 15 AN: 86254

European-Finnish (FIN) AF: 0.000693 AC: 37 AN: 53366

Middle Eastern (MID) AF: 0.00330 AC: 19 AN: 5766

European-Non Finnish (NFE) AF: 0.000255 AC: 284 AN: 1111970

Other (OTH) AF: 0.00424 AC: 256 AN: 60394

GnomAD4 genome AF: 0.0161 AC: 2451 AN: 152312 Hom.: 58 Cov.: 32 AF XY: 0.0148 AC XY: 1103 AN XY: 74480

African (AFR) AF: 0.0547 AC: 2273 AN: 41560

American (AMR) AF: 0.00706 AC: 108 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.000377 AC: 4 AN: 10624

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000367 AC: 25 AN: 68032

Other (OTH) AF: 0.0175 AC: 37 AN: 2114

Alfa AF: 0.00923 Hom.: 12

Bravo AF: 0.0194

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000474

ClinVar

ClinVar submissions

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
BayesDel_noAF	Benign	-0.74
CADD	Benign	11
DANN	Benign	0.64
PhyloP100		0.38
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=66/34	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000032
dbscSNV1_RF	Benign	0.0060
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: rs114219049; hg19: chr20-3838462;