Menu
GeneBe

rs61732425

chr16-3254735-C-T

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_000243.3(MEFV):c.333G>A(p.Gly111=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000593 in 1,612,880 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0032 ( 3 hom., cov: 34)
Exomes 𝑓: 0.00033 ( 2 hom. )

Consequence

MEFV
NM_000243.3 synonymous

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:11O:1

Conservation

PhyloP100: 0.201
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 16-3254735-C-T is Benign according to our data. Variant chr16-3254735-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 97517.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-3254735-C-T is described in Lovd as [Benign].
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.201 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 3 SD gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MEFVNM_000243.3 linkuse as main transcriptc.333G>A p.Gly111= synonymous_variant 2/10 ENST00000219596.6
MEFVNM_001198536.2 linkuse as main transcriptc.277+1576G>A intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MEFVENST00000219596.6 linkuse as main transcriptc.333G>A p.Gly111= synonymous_variant 2/101 NM_000243.3 P3O15553-2

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00316
AC:
481
AN:
152252
Hom.:
3
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.0106
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00190
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:
0.000132
Gnomad OTH
AF:
0.00239
GnomAD3 exomes
AF:
0.000796
AC:
197
AN:
247392
Hom.:
0
AF XY:
0.000586
AC XY:
79
AN XY:
134840
show subpopulations
Gnomad AFR exome
AF:
0.0102
Gnomad AMR exome
AF:
0.000810
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000630
Gnomad OTH exome
AF:
0.000822
GnomAD4 exome
AF:
0.000325
AC:
475
AN:
1460510
Hom.:
2
Cov.:
65
AF XY:
0.000261
AC XY:
190
AN XY:
726586
show subpopulations
Gnomad4 AFR exome
AF:
0.0108
Gnomad4 AMR exome
AF:
0.000984
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000261
Gnomad4 OTH exome
AF:
0.000646
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00316
AC:
481
AN:
152370
Hom.:
3
Cov.:
34
AF XY:
0.00293
AC XY:
218
AN XY:
74508
show subpopulations
Gnomad4 AFR
AF:
0.0105
Gnomad4 AMR
AF:
0.00190
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000132
Gnomad4 OTH
AF:
0.00237
Alfa
AF:
0.00156
Hom.:
0
Bravo
AF:
0.00345
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.0000593

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:11Other:1
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Familial Mediterranean fever Benign:3Other:1
Likely benign, no assertion criteria providedclinical testingNatera, Inc.Dec 09, 2019- -
not provided, no classification providedliterature onlyUnité médicale des maladies autoinflammatoires, CHRU Montpellier-- -
Likely benign, criteria provided, single submitterclinical testingGenome-Nilou LabFeb 08, 2023- -
Benign, criteria provided, single submitterclinical testingInvitaeJan 30, 2024- -
not specified Benign:2
Likely benign, criteria provided, single submitterclinical testingWomen's Health and Genetics/Laboratory Corporation of America, LabCorpJul 10, 2020- -
Benign, criteria provided, single submitterclinical testingEurofins Ntd Llc (ga)Jun 29, 2017- -
not provided Benign:2
Likely benign, criteria provided, single submitterclinical testingARUP Laboratories, Molecular Genetics and Genomics, ARUP LaboratoriesJul 26, 2017The MEFV c.333G>A;p.Gly111Gly variant has not been described in the medical literature, but is listed in a gene-specific database in a symptomatic individual (see link). The variant is listed in the ClinVar database (Variation ID: 97517) and the dbSNP variant database (rs61732425) with an allele frequency of up to 0.7373 percent (32/4308 alleles) in the African American population in the Exome Variant Server and up to 1.081 percent in the African population in the Genome Aggregation Consortium (251/23226 alleles, 2 homozygotes). The nucleotide at this position is weakly conserved and computational algorithms (SpliceSiteFinder-like, MaxEntScan, NNSplice, GeneSplicer, Human Splicing Finder) predict this variant does not significantly alter splicing. Considering available information, this variant is classified as likely benign. References: Link to Infevers database: http://fmf.igh.cnrs.fr/ISSAID/infevers/search.php?n=1 -
Benign, criteria provided, single submitterclinical testingGeneDxMar 03, 2015- -
Acute febrile neutrophilic dermatosis Benign:1
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabFeb 08, 2023- -
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsApr 01, 2022This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Familial Mediterranean fever, autosomal dominant Benign:1
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabFeb 08, 2023- -
Autoinflammatory syndrome Benign:1
Likely benign, criteria provided, single submitterclinical testingGenome Diagnostics Laboratory, The Hospital for Sick ChildrenNov 16, 2020- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.78
Cadd
Benign
2.0
Dann
Benign
0.51

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

LitVar

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

Other links and lift over

dbSNP: rs61732425; hg19: chr16-3304735; COSMIC: COSV54822084; API