Genetic Variant NM_020746.5:c.*5157T>C (chr20-3871304-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_020746.5(MAVS):c.*5157T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.362 in 153,774 control chromosomes in the GnomAD database, including 11,452 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 0.36 ( 11275 hom., cov: 32)

Exomes 𝑓: 0.46 ( 177 hom. )

Consequence

MAVS
NM_020746.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.882

Publications

14 publications found

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:

PANK2-AS1 (HGNC:40732): (PANK2 antisense RNA 1)

PANK2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
MAVS	NM_020746.5 link	c.*5157T>C	3_prime_UTR_variant	Exon 7 of 7	ENST00000428216.4	NP_065797.2	Q7Z434-1
MAVS	NR_037921.2 link	n.6744T>C	non_coding_transcript_exon_variant	Exon 6 of 6
MAVS	NM_001206491.2 link	c.*5157T>C	3_prime_UTR_variant	Exon 6 of 6		NP_001193420.1	Q7Z434-4
MAVS	NM_001385663.1 link	c.*5157T>C	3_prime_UTR_variant	Exon 8 of 8		NP_001372592.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MAVS	ENST00000428216.4 link	c.*5157T>C	3_prime_UTR_variant	Exon 7 of 7	1	NM_020746.5	ENSP00000401980.2	Q7Z434-1
MAVS	ENST00000416600.6 link	c.*5157T>C	3_prime_UTR_variant	Exon 6 of 6	1		ENSP00000413749.2	Q7Z434-4
PANK2-AS1	ENST00000725518.1 link	n.426-8414A>G	intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.361

AC:

54913

AN:

151958

Hom.:

11271

Cov.:

show subpopulations

Gnomad AFR

AF:

0.160

Gnomad AMI

AF:

0.546

Gnomad AMR

AF:

0.406

Gnomad ASJ

AF:

0.375

Gnomad EAS

AF:

0.225

Gnomad SAS

AF:

0.395

Gnomad FIN

AF:

0.477

Gnomad MID

AF:

0.408

Gnomad NFE

AF:

0.460

Gnomad OTH

AF:

0.374

GnomAD4 exome

AF:

0.463

AC:

786

AN:

1698

Hom.:

177

Cov.:

AF XY:

0.431

AC XY:

383

AN XY:

888

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.423

AC:

AN:

130

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.465

AC:

711

AN:

1528

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.545

AC:

AN:

Other (OTH)

AF:

0.438

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

112

140

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.361

AC:

54922

AN:

152076

Hom.:

11275

Cov.:

AF XY:

0.362

AC XY:

26883

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.160

AC:

6627

AN:

41516

American (AMR)

AF:

0.407

AC:

6200

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.375

AC:

1299

AN:

3466

East Asian (EAS)

AF:

0.224

AC:

1160

AN:

5170

South Asian (SAS)

AF:

0.396

AC:

1905

AN:

4816

European-Finnish (FIN)

AF:

0.477

AC:

5044

AN:

10564

Middle Eastern (MID)

AF:

0.395

AC:

116

AN:

294

European-Non Finnish (NFE)

AF:

0.460

AC:

31287

AN:

67980

Other (OTH)

AF:

0.373

AC:

787

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1693

3386

5079

6772

8465

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

534

1068

1602

2136

2670

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.427

Hom.:

18882

Bravo

AF:

0.350

Asia WGS

AF:

0.326

AC:

1131

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

8.1

(source)

DANN

Benign

0.91

PhyloP100

-0.88

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over