Variant rs1231124 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_000243.3(MEFV):c.1611-90C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.421 in 945,006 control chromosomes in the GnomAD database, including 86,632 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.41 ( 12998 hom., cov: 32)

Exomes 𝑓: 0.42 ( 73634 hom. )

Consequence

MEFV
NM_000243.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.06

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 (BayesDel_noAF=-0.87).

BP6

Variant 16-3244678-G-A is Benign according to our data. Variant chr16-3244678-G-A is described in ClinVar as [Benign]. Clinvar id is 676934.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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.1611-90C>T		intron_variant		ENST00000219596.6
MEFV	NM_001198536.2 linkuse as main transcript	c.978-90C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MEFV	ENST00000219596.6 linkuse as main transcript	c.1611-90C>T		intron_variant		1	NM_000243.3	P3	O15553-2

Frequencies

GnomAD3 genomes

AF:

0.409

AC:

62069

AN:

151852

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:

0.386

Gnomad SAS

AF:

0.271

Gnomad FIN

AF:

0.441

Gnomad MID

AF:

0.475

Gnomad NFE

AF:

0.461

Gnomad OTH

AF:

0.424

GnomAD4 exome

AF:

0.423

AC:

335835

AN:

793036

Hom.:

73634

AF XY:

0.420

AC XY:

176019

AN XY:

419218

show subpopulations

Gnomad4 AFR exome

AF:

0.341

Gnomad4 AMR exome

AF:

0.274

Gnomad4 ASJ exome

AF:

0.442

Gnomad4 EAS exome

AF:

0.386

Gnomad4 SAS exome

AF:

0.287

Gnomad4 FIN exome

AF:

0.440

Gnomad4 NFE exome

AF:

0.458

Gnomad4 OTH exome

AF:

0.428

GnomAD4 genome

AF:

0.409

AC:

62087

AN:

151970

Hom.:

12998

Cov.:

AF XY:

0.404

AC XY:

30039

AN XY:

74276

show subpopulations

Gnomad4 AFR

AF:

0.338

Gnomad4 AMR

AF:

0.375

Gnomad4 ASJ

AF:

0.436

Gnomad4 EAS

AF:

0.386

Gnomad4 SAS

AF:

0.273

Gnomad4 FIN

AF:

0.441

Gnomad4 NFE

AF:

0.461

Gnomad4 OTH

AF:

0.423

Alfa

AF:

0.431

Hom.:

1778

Bravo

AF:

0.400

Asia WGS

AF:

0.307

AC:

1068

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 44% of patients studied by a panel of primary immunodeficiencies. Number of patients: 42. Only high quality variants are reported. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Familial Mediterranean fever, autosomal dominant

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 01, 2021

- -

Familial Mediterranean fever

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_noAF

Benign

-0.87

CADD

Benign

0.50

DANN

Benign

0.55

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.

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