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 ENST00000956137.1(MEFV):c.*1171G>T variant causes a 3 prime UTR 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
ENST00000956137.1 3_prime_UTR

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):

autosomal recessive familial Mediterranean fever
Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
familial Mediterranean fever
Inheritance: AR, AD, SD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Myriad Women's Health, Orphanet, ClinGen
familial Mediterranean fever, autosomal dominant
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

MEFV links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript ENST00000956137.1, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000956137.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEFV	NM_000243.3	MANE Select	c.*1171G>T		downstream_gene	N/A	NP_000234.1	O15553-2
	MEFV	NM_001198536.2		c.*1721G>T		downstream_gene	N/A	NP_001185465.2	O15553-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MEFV	ENST00000956137.1		c.*1171G>T	3_prime_UTR	Exon 10 of 10	ENSP00000626196.1
MEFV	ENST00000219596.6	TSL:1 MANE Select	c.*1171G>T	downstream_gene	N/A	ENSP00000219596.1	O15553-2
MEFV	ENST00000339854.8	TSL:5	c.*1171G>T	downstream_gene	N/A	ENSP00000339639.4	F8W6Z2

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 v4.9

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over