Variant chr20-3857812-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_020746.5(MAVS):c.292+3G>A variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00132 in 1,614,134 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0073 ( 15 hom., cov: 32)

Exomes 𝑓: 0.00069 ( 8 hom. )

Consequence

MAVS
NM_020746.5 splice_donor_region, intron

Scores

Splicing: ADA: 0.00003007

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.250

Variant links:

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]

MAVS links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 20-3857812-G-A is Benign according to our data. Variant chr20-3857812-G-A is described in ClinVar as [Benign]. Clinvar id is 718324.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00731 (1114/152314) while in subpopulation AFR AF= 0.0249 (1035/41566). AF 95% confidence interval is 0.0236. There are 15 homozygotes in gnomad4. There are 519 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1114 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
MAVS	NM_020746.5 linkuse as main transcript	c.292+3G>A	splice_donor_region_variant, intron_variant	ENST00000428216.4
MAVS	NM_001206491.2 linkuse as main transcript	c.-132+3071G>A	intron_variant
MAVS	NM_001385663.1 linkuse as main transcript	c.-256+3G>A	splice_donor_region_variant, intron_variant
MAVS	NR_037921.2 linkuse as main transcript	n.429+3G>A	splice_donor_region_variant, intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAVS	ENST00000428216.4 linkuse as main transcript	c.292+3G>A		splice_donor_region_variant, intron_variant		1	NM_020746.5	P1	Q7Z434-1
MAVS	ENST00000416600.6 linkuse as main transcript	c.-132+3071G>A		intron_variant		1			Q7Z434-4

Frequencies

GnomAD3 genomes

AF:

0.00731

AC:

1112

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0249

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00367

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00813

GnomAD3 exomes

AF:

0.00174

AC:

438

AN:

251364

Hom.:

AF XY:

0.00131

AC XY:

178

AN XY:

135868

show subpopulations

Gnomad AFR exome

AF:

0.0236

Gnomad AMR exome

AF:

0.000983

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000106

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.000692

AC:

1011

AN:

1461820

Hom.:

Cov.:

AF XY:

0.000575

AC XY:

418

AN XY:

727214

show subpopulations

Gnomad4 AFR exome

AF:

0.0243

Gnomad4 AMR exome

AF:

0.00145

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000207

Gnomad4 OTH exome

AF:

0.00167

GnomAD4 genome

AF:

0.00731

AC:

1114

AN:

152314

Hom.:

Cov.:

AF XY:

0.00697

AC XY:

519

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.0249

Gnomad4 AMR

AF:

0.00366

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00804

Alfa

AF:

0.00324

Hom.:

Bravo

AF:

0.00813

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Mar 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000030

dbscSNV1_RF

Benign

0.0020

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over