chr16-3247100-G-A

Position:

chr16-3247100-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The ENST00000219596.6(MEFV):c.1503C>T(p.Arg501=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0068 in 1,614,126 control chromosomes in the GnomAD database, including 300 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0087 ( 30 hom., cov: 33)

Exomes 𝑓: 0.0066 ( 270 hom. )

Consequence

MEFV
ENST00000219596.6 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:12O:1

Conservation

PhyloP100: -4.40

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 16-3247100-G-A is Benign according to our data. Variant chr16-3247100-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 36501.We mark this variant Likely_benign, oryginal submissions are: {Benign=8, Likely_benign=2, Uncertain_significance=1, not_provided=1}. Variant chr16-3247100-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-4.4 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0936 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MEFV	NM_000243.3 linkuse as main transcript	c.1503C>T	p.Arg501=	synonymous_variant	5/10	ENST00000219596.6	NP_000234.1
MEFV	NM_001198536.2 linkuse as main transcript	c.870C>T	p.Arg290=	synonymous_variant	4/9		NP_001185465.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MEFV	ENST00000219596.6 linkuse as main transcript	c.1503C>T	p.Arg501=	synonymous_variant	5/10	1	NM_000243.3	ENSP00000219596	P3	O15553-2

Frequencies

GnomAD3 genomes

AF:

0.00867

AC:

1319

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00437

Gnomad AMI

AF:

0.0274

Gnomad AMR

AF:

0.0117

Gnomad ASJ

AF:

0.0173

Gnomad EAS

AF:

0.101

Gnomad SAS

AF:

0.0172

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00341

Gnomad OTH

AF:

0.0143

GnomAD3 exomes

AF:

0.0125

AC:

3139

AN:

251492

Hom.:

132

AF XY:

0.0127

AC XY:

1728

AN XY:

135922

show subpopulations

Gnomad AFR exome

AF:

0.00369

Gnomad AMR exome

AF:

0.00405

Gnomad ASJ exome

AF:

0.0176

Gnomad EAS exome

AF:

0.104

Gnomad SAS exome

AF:

0.0145

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.00301

Gnomad OTH exome

AF:

0.00993

GnomAD4 exome

AF:

0.00661

AC:

9662

AN:

1461842

Hom.:

270

Cov.:

AF XY:

0.00683

AC XY:

4970

AN XY:

727218

show subpopulations

Gnomad4 AFR exome

AF:

0.00352

Gnomad4 AMR exome

AF:

0.00387

Gnomad4 ASJ exome

AF:

0.0179

Gnomad4 EAS exome

AF:

0.0877

Gnomad4 SAS exome

AF:

0.0150

Gnomad4 FIN exome

AF:

0.000337

Gnomad4 NFE exome

AF:

0.00285

Gnomad4 OTH exome

AF:

0.0147

GnomAD4 genome

AF:

0.00865

AC:

1318

AN:

152284

Hom.:

Cov.:

AF XY:

0.00935

AC XY:

696

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.00431

Gnomad4 AMR

AF:

0.0117

Gnomad4 ASJ

AF:

0.0173

Gnomad4 EAS

AF:

0.101

Gnomad4 SAS

AF:

0.0178

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00341

Gnomad4 OTH

AF:

0.0147

Alfa

AF:

0.00477

Hom.:

Bravo

AF:

0.00941

Asia WGS

AF:

0.0610

AC:

212

AN:

3478

EpiCase

AF:

0.00463

EpiControl

AF:

0.00439

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:12Other:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Familial Mediterranean fever

Uncertain:1Benign:4Other:1

Benign, no assertion criteria provided	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	May 23, 2011	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Feb 08, 2023	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -
not provided, no classification provided	literature only	Unité médicale des maladies autoinflammatoires, CHRU Montpellier	-	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Apr 27, 2017	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	This variant is associated with the following publications: (PMID: 32199921) -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Oct 26, 2023	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Acute febrile neutrophilic dermatosis

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Feb 08, 2023

- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 07, 2016

This alteration is classified as 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

Likely benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Feb 08, 2023

- -

Autoinflammatory syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Mar 12, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.53

DANN

Benign

0.43

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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