16-3242874-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000243.3(MEFV):c.*267G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.585 in 501,962 control chromosomes in the GnomAD database, including 87,421 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.59 ( 26841 hom., cov: 30)

Exomes 𝑓: 0.58 ( 60580 hom. )

Consequence

MEFV
NM_000243.3 3_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.0270

Publications

11 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 16-3242874-C-T is Benign according to our data. Variant chr16-3242874-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 224065.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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.*267G>A		3_prime_UTR_variant	Exon 10 of 10	ENST00000219596.6	NP_000234.1	O15553-2
MEFV	NM_001198536.2 link	c.*817G>A		3_prime_UTR_variant	Exon 9 of 9		NP_001185465.2	O15553-3D2DTW2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEFV	ENST00000219596.6 link	c.*267G>A		3_prime_UTR_variant	Exon 10 of 10	1	NM_000243.3	ENSP00000219596.1		O15553-2

Frequencies

GnomAD3 genomes

AF:

0.591

AC:

89647

AN:

151578

Hom.:

26799

Cov.:

show subpopulations

Gnomad AFR

AF:

0.662

Gnomad AMI

AF:

0.400

Gnomad AMR

AF:

0.625

Gnomad ASJ

AF:

0.564

Gnomad EAS

AF:

0.615

Gnomad SAS

AF:

0.728

Gnomad FIN

AF:

0.560

Gnomad MID

AF:

0.516

Gnomad NFE

AF:

0.539

Gnomad OTH

AF:

0.576

GnomAD4 exome

AF:

0.583

AC:

204090

AN:

350264

Hom.:

60580

Cov.:

AF XY:

0.590

AC XY:

109942

AN XY:

186302

show subpopulations

African (AFR)

AF:

0.661

AC:

6832

AN:

10336

American (AMR)

AF:

0.694

AC:

10969

AN:

15814

Ashkenazi Jewish (ASJ)

AF:

0.561

AC:

5945

AN:

10606

East Asian (EAS)

AF:

0.618

AC:

13356

AN:

21600

South Asian (SAS)

AF:

0.710

AC:

31864

AN:

44910

European-Finnish (FIN)

AF:

0.560

AC:

10614

AN:

18964

Middle Eastern (MID)

AF:

0.536

AC:

799

AN:

1490

European-Non Finnish (NFE)

AF:

0.543

AC:

112410

AN:

206868

Other (OTH)

AF:

0.574

AC:

11301

AN:

19676

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

4349

8698

13047

17396

21745

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

652

1304

1956

2608

3260

<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:

0.592

AC:

89750

AN:

151698

Hom.:

26841

Cov.:

AF XY:

0.596

AC XY:

44163

AN XY:

74114

show subpopulations

African (AFR)

AF:

0.663

AC:

27399

AN:

41340

American (AMR)

AF:

0.625

AC:

9515

AN:

15224

Ashkenazi Jewish (ASJ)

AF:

0.564

AC:

1958

AN:

3470

East Asian (EAS)

AF:

0.614

AC:

3162

AN:

5148

South Asian (SAS)

AF:

0.727

AC:

3497

AN:

4810

European-Finnish (FIN)

AF:

0.560

AC:

5864

AN:

10474

Middle Eastern (MID)

AF:

0.500

AC:

145

AN:

290

European-Non Finnish (NFE)

AF:

0.539

AC:

36629

AN:

67924

Other (OTH)

AF:

0.577

AC:

1218

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1845

3690

5534

7379

9224

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:

0.567

Hom.:

11555

Bravo

AF:

0.600

Asia WGS

AF:

0.692

AC:

2407

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Familial Mediterranean fever

Benign:3

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Feb 08, 2023

Genome-Nilou Lab

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 25, 2016

Atomic Energy Commission of Syria (AECS)

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:case-control

- -

not provided

Benign:2

Jun 14, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Acute febrile neutrophilic dermatosis

Benign:1

Feb 08, 2023

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Familial Mediterranean fever, autosomal dominant

Benign:1

Feb 08, 2023

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

2.6

(source)

DANN

Benign

0.47

PhyloP100

0.027

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over