Genetic Variant MEFV:c.*1171G>T (chr16-3241970-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000243.3(MEFV):c.*1171G>T variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.592 in 152,858 control chromosomes in the GnomAD database, including 27,082 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.59 ( 26899 hom., cov: 33)

Exomes 𝑓: 0.67 ( 183 hom. )

Consequence

MEFV
NM_000243.3 downstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0370

Publications

13 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.707 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEFV	NM_000243.3 link	c.*1171G>T		downstream_gene_variant		ENST00000219596.6	NP_000234.1	O15553-2
MEFV	NM_001198536.2 link	c.*1721G>T		downstream_gene_variant			NP_001185465.2	O15553-3D2DTW2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEFV	ENST00000219596.6 link	c.*1171G>T		downstream_gene_variant		1	NM_000243.3	ENSP00000219596.1		O15553-2

Frequencies

GnomAD3 genomes

AF:

0.591

AC:

89821

AN:

151920

Hom.:

26858

Cov.:

show subpopulations

Gnomad AFR

AF:

0.662

Gnomad AMI

AF:

0.402

Gnomad AMR

AF:

0.625

Gnomad ASJ

AF:

0.564

Gnomad EAS

AF:

0.614

Gnomad SAS

AF:

0.729

Gnomad FIN

AF:

0.559

Gnomad MID

AF:

0.525

Gnomad NFE

AF:

0.539

Gnomad OTH

AF:

0.576

GnomAD4 exome

AF:

0.670

AC:

549

AN:

820

Hom.:

183

AF XY:

0.694

AC XY:

412

AN XY:

594

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.375

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AF:

0.711

AC:

378

AN:

532

European-Finnish (FIN)

AF:

0.639

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.607

AC:

119

AN:

196

Other (OTH)

AF:

0.625

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.527

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.591

AC:

89922

AN:

152038

Hom.:

26899

Cov.:

AF XY:

0.596

AC XY:

44265

AN XY:

74296

show subpopulations

African (AFR)

AF:

0.662

AC:

27454

AN:

41464

American (AMR)

AF:

0.625

AC:

9537

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.564

AC:

1959

AN:

3472

East Asian (EAS)

AF:

0.614

AC:

3175

AN:

5170

South Asian (SAS)

AF:

0.727

AC:

3508

AN:

4822

European-Finnish (FIN)

AF:

0.559

AC:

5906

AN:

10556

Middle Eastern (MID)

AF:

0.510

AC:

149

AN:

292

European-Non Finnish (NFE)

AF:

0.539

AC:

36650

AN:

67984

Other (OTH)

AF:

0.577

AC:

1217

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1894

3788

5682

7576

9470

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

762

1524

2286

3048

3810

<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:

0.558

Hom.:

40055

Bravo

AF:

0.599

Asia WGS

AF:

0.692

AC:

2406

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.52

(source)

DANN

Benign

0.39

PhyloP100

0.037

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over