16-3254463-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000243.3(MEFV):c.605G>A(p.Arg202Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 1,602,838 control chromosomes in the GnomAD database, including 49,745 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 4074 hom., cov: 33)

Exomes 𝑓: 0.24 ( 45671 hom. )

Consequence

MEFV
NM_000243.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts U:1B:13

Conservation

PhyloP100: -2.58

Publications

215 publications found

Variant links:

Genes affected

MEFV (HGNC:6998): (MEFV innate immunity regulator, pyrin) This gene encodes a protein, also known as pyrin or marenostrin, that is an important modulator of innate immunity. Mutations in this gene are associated with Mediterranean fever, a hereditary periodic fever syndrome. [provided by RefSeq, Jul 2008]

MEFV Gene-Disease associations (from GenCC):

familial Mediterranean fever
Inheritance: AD, AR, SD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, Myriad Women’s Health, ClinGen
autosomal recessive familial Mediterranean fever
Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
familial Mediterranean fever, autosomal dominant
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

MEFV links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00396502).

BP6

Variant 16-3254463-C-T is Benign according to our data. Variant chr16-3254463-C-T is described in ClinVar as Benign. ClinVar VariationId is 36512.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000243.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEFV	NM_000243.3	MANE Select	c.605G>A	p.Arg202Gln	missense	Exon 2 of 10	NP_000234.1
	MEFV	NM_001198536.2		c.277+1848G>A		intron	N/A	NP_001185465.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
MEFV	ENST00000219596.6	TSL:1 MANE Select	c.605G>A	p.Arg202Gln	missense	Exon 2 of 10	ENSP00000219596.1
MEFV	ENST00000541159.5	TSL:1	c.277+1848G>A		intron	N/A	ENSP00000438711.1
MEFV	ENST00000570511.5	TSL:1	n.605G>A		non_coding_transcript_exon	Exon 2 of 6	ENSP00000458312.1

Frequencies

GnomAD3 genomes

AF:

0.206

AC:

31329

AN:

152092

Hom.:

4075

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0691

Gnomad AMI

AF:

0.280

Gnomad AMR

AF:

0.301

Gnomad ASJ

AF:

0.214

Gnomad EAS

AF:

0.0378

Gnomad SAS

AF:

0.0998

Gnomad FIN

AF:

0.343

Gnomad MID

AF:

0.156

Gnomad NFE

AF:

0.266

Gnomad OTH

AF:

0.213

GnomAD2 exomes

AF:

0.238

AC:

54494

AN:

229238

AF XY:

0.230

show subpopulations

Gnomad AFR exome

AF:

0.0651

Gnomad AMR exome

AF:

0.362

Gnomad ASJ exome

AF:

0.226

Gnomad EAS exome

AF:

0.0432

Gnomad FIN exome

AF:

0.350

Gnomad NFE exome

AF:

0.272

Gnomad OTH exome

AF:

0.250

GnomAD4 exome

AF:

0.243

AC:

352124

AN:

1450630

Hom.:

45671

Cov.:

AF XY:

0.239

AC XY:

172063

AN XY:

720704

show subpopulations

African (AFR)

AF:

0.0618

AC:

2044

AN:

33072

American (AMR)

AF:

0.349

AC:

15228

AN:

43580

Ashkenazi Jewish (ASJ)

AF:

0.223

AC:

5765

AN:

25904

East Asian (EAS)

AF:

0.0370

AC:

1461

AN:

39534

South Asian (SAS)

AF:

0.105

AC:

9039

AN:

85900

European-Finnish (FIN)

AF:

0.337

AC:

16974

AN:

50336

Middle Eastern (MID)

AF:

0.146

AC:

764

AN:

5224

European-Non Finnish (NFE)

AF:

0.260

AC:

287666

AN:

1107298

Other (OTH)

AF:

0.221

AC:

13183

AN:

59782

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

16008

32017

48025

64034

80042

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9382

18764

28146

37528

46910

<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:

0.206

AC:

31324

AN:

152208

Hom.:

4074

Cov.:

AF XY:

0.210

AC XY:

15601

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.0689

AC:

2864

AN:

41578

American (AMR)

AF:

0.301

AC:

4610

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.214

AC:

741

AN:

3466

East Asian (EAS)

AF:

0.0379

AC:

196

AN:

5168

South Asian (SAS)

AF:

0.0996

AC:

481

AN:

4828

European-Finnish (FIN)

AF:

0.343

AC:

3635

AN:

10612

Middle Eastern (MID)

AF:

0.158

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.266

AC:

18056

AN:

67940

Other (OTH)

AF:

0.208

AC:

441

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1229

2459

3688

4918

6147

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

326

652

978

1304

1630

<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:

0.244

Hom.:

1192

Bravo

AF:

0.200

TwinsUK

AF:

0.249

AC:

925

ALSPAC

AF:

0.241

AC:

930

ESP6500AA

AF:

0.0651

AC:

280

ESP6500EA

AF:

0.240

AC:

1996

ExAC

AF:

0.223

AC:

26172

Asia WGS

AF:

0.0730

AC:

257

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Familial Mediterranean fever (4)

not specified (4)

not provided (3)

Autoinflammatory syndrome (1)

Familial Mediterranean fever, autosomal dominant (1)

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.0040

(source)

DANN

Benign

0.44

DEOGEN2

Benign

0.26

Eigen

Benign

-2.2

Eigen_PC

Benign

-2.2

FATHMM_MKL

Benign

0.0032

LIST_S2

Benign

0.16

MetaRNN

Benign

0.0040

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.60

PhyloP100

-2.6

PrimateAI

Benign

0.31

PROVEAN

Benign

0.30

REVEL

Benign

0.033

Sift

Benign

1.0

Sift4G

Benign

0.73

Polyphen

0.0020

Vest4

0.048

MPC

0.13

ClinPred

0.00059

GERP RS

-5.2

Varity_R

0.017

gMVP

0.22

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over