16-3243888-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000541159.5(MEFV):c.1306G>A(p.Gly436Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.432 in 1,612,752 control chromosomes in the GnomAD database, including 153,596 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.41 ( 12998 hom., cov: 31)

Exomes 𝑓: 0.43 ( 140598 hom. )

Consequence

MEFV
ENST00000541159.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: -0.206

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=6.046295E-4).

BP6

Variant 16-3243888-C-T is Benign according to our data. Variant chr16-3243888-C-T is described in ClinVar as [Benign]. Clinvar id is 36505.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-3243888-C-T is described in Lovd as [Benign]. Variant chr16-3243888-C-T is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MEFV	NM_000243.3 linkuse as main transcript	c.1764G>A	p.Pro588=	synonymous_variant	9/10	ENST00000219596.6
MEFV	NM_001198536.2 linkuse as main transcript	c.1306G>A	p.Gly436Arg	missense_variant	8/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MEFV	ENST00000219596.6 linkuse as main transcript	c.1764G>A	p.Pro588=	synonymous_variant	9/10	1	NM_000243.3	P3	O15553-2

Frequencies

GnomAD3 genomes

AF:

0.409

AC:

62069

AN:

151778

Hom.:

12999

Cov.:

show subpopulations

Gnomad AFR

AF:

0.338

Gnomad AMI

AF:

0.599

Gnomad AMR

AF:

0.375

Gnomad ASJ

AF:

0.436

Gnomad EAS

AF:

0.387

Gnomad SAS

AF:

0.271

Gnomad FIN

AF:

0.442

Gnomad MID

AF:

0.481

Gnomad NFE

AF:

0.461

Gnomad OTH

AF:

0.426

GnomAD3 exomes

AF:

0.392

AC:

98072

AN:

250496

Hom.:

20196

AF XY:

0.396

AC XY:

53683

AN XY:

135460

show subpopulations

Gnomad AFR exome

AF:

0.341

Gnomad AMR exome

AF:

0.261

Gnomad ASJ exome

AF:

0.444

Gnomad EAS exome

AF:

0.378

Gnomad SAS exome

AF:

0.272

Gnomad FIN exome

AF:

0.429

Gnomad NFE exome

AF:

0.459

Gnomad OTH exome

AF:

0.431

GnomAD4 exome

AF:

0.434

AC:

634285

AN:

1460856

Hom.:

140598

Cov.:

AF XY:

0.432

AC XY:

313647

AN XY:

726710

show subpopulations

Gnomad4 AFR exome

AF:

0.333

Gnomad4 AMR exome

AF:

0.272

Gnomad4 ASJ exome

AF:

0.440

Gnomad4 EAS exome

AF:

0.386

Gnomad4 SAS exome

AF:

0.286

Gnomad4 FIN exome

AF:

0.436

Gnomad4 NFE exome

AF:

0.457

Gnomad4 OTH exome

AF:

0.428

GnomAD4 genome

AF:

0.409

AC:

62086

AN:

151896

Hom.:

12998

Cov.:

AF XY:

0.404

AC XY:

30014

AN XY:

74204

show subpopulations

Gnomad4 AFR

AF:

0.338

Gnomad4 AMR

AF:

0.375

Gnomad4 ASJ

AF:

0.436

Gnomad4 EAS

AF:

0.388

Gnomad4 SAS

AF:

0.272

Gnomad4 FIN

AF:

0.442

Gnomad4 NFE

AF:

0.461

Gnomad4 OTH

AF:

0.424

Alfa

AF:

0.446

Hom.:

31246

Bravo

AF:

0.400

TwinsUK

AF:

0.456

AC:

1691

ALSPAC

AF:

0.458

AC:

1767

ESP6500AA

AF:

0.342

AC:

1501

ESP6500EA

AF:

0.465

AC:

4003

ExAC

AF:

0.394

AC:

47781

Asia WGS

AF:

0.307

AC:

1068

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Familial Mediterranean fever

Benign:5

Benign, criteria provided, single submitter	clinical testing;curation	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Aug 18, 2011	- -
Benign, criteria provided, single submitter	literature only	Counsyl	Jan 14, 2015	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Nov 19, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 01, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Dec 14, 2015	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Jul 05, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Nov 12, 2023	This variant is classified as Benign based on local population frequency. This variant was detected in 63% of patients studied by a panel of primary immunodeficiencies. Number of patients: 60. Only high quality variants are reported. -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Dec 01, 2023	MEFV: BP7, BS1, BS2 -
Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

Familial Mediterranean fever, autosomal dominant

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 01, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.32

Cadd

Benign

Dann

Benign

0.28

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.0023

LIST_S2

Benign

0.27

MetaRNN

Benign

0.00060

MetaSVM

Benign

-0.95

MutationTaster

Benign

1.0

P;P;P;P

PROVEAN

Benign

1.7

REVEL

Benign

0.044

Sift

Benign

1.0

Sift4G

Benign

0.76

Vest4

0.16

MutPred

0.30

Gain of MoRF binding (P = 0.0046);

ClinPred

0.0021

GERP RS

-0.23

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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