20-3849815-C-T

Variant names:

• chr20-3849815-C-T
• rs6084496
• NM_020746.5:c.-68+2912C>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.-68+2912C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0657 in 152,196 control chromosomes in the GnomAD database, including 478 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 0.066 (478 hom., cov: 32)
• Consequence: MAVS NM_020746.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.897
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.128 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.-68+2912C>T		intron	N/A	NP_065797.2	Q7Z434-1
	MAVS	NM_001206491.2		c.-316+2912C>T		intron	N/A	NP_001193420.1	Q7Z434-4
	MAVS	NM_001385663.1		c.-615+2912C>T		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.-68+2912C>T		intron	N/A	ENSP00000401980.2	Q7Z434-1
	MAVS	ENST00000416600.6	TSL:1	c.-316+2912C>T		intron	N/A	ENSP00000413749.2	Q7Z434-4
	MAVS	ENST00000883969.1		c.-201-2027C>T		intron	N/A	ENSP00000554028.1

Frequencies

GnomAD3 genomes AF: 0.0656 AC: 9975 AN: 152078 Hom.: 476 Cov.: 32

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0338

Gnomad ASJ AF: 0.0565

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.0769

Gnomad FIN AF: 0.0576

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0312

Gnomad OTH AF: 0.0698

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0657 AC: 9992 AN: 152196 Hom.: 478 Cov.: 32 AF XY: 0.0670 AC XY: 4987 AN XY: 74416

African (AFR) AF: 0.131 AC: 5423 AN: 41506

American (AMR) AF: 0.0339 AC: 517 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.0565 AC: 196 AN: 3472

East Asian (EAS) AF: 0.111 AC: 578 AN: 5186

South Asian (SAS) AF: 0.0776 AC: 374 AN: 4822

European-Finnish (FIN) AF: 0.0576 AC: 611 AN: 10608

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0312 AC: 2121 AN: 68018

Other (OTH) AF: 0.0700 AC: 148 AN: 2114

Alfa AF: 0.0436 Hom.: 573

Bravo AF: 0.0671

Asia WGS AF: 0.103 AC: 357 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.32
DANN	Benign	0.45
PhyloP100		-0.90
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: rs6084496; hg19: chr20-3830462;