dbSNP rs224234: 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

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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