Genetic Variant MEFV:c.*836_*837insACT (chr16-3242304-C-CAGT) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_000243.3(MEFV):c.*836_*837insACT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.59 ( 26119 hom., cov: 0)

Exomes 𝑓: 0.58 ( 1257 hom. )

Consequence

MEFV
NM_000243.3 3_prime_UTR

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.355

Publications

0 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 -10 ACMG points.

BP6

Variant 16-3242304-C-CAGT is Benign according to our data. Variant chr16-3242304-C-CAGT is described in ClinVar as [Likely_benign]. Clinvar id is 319088.Status of the report is criteria_provided_single_submitter, 1 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.836_837insACT		3_prime_UTR_variant	Exon 10 of 10	ENST00000219596.6	NP_000234.1	O15553-2
MEFV	NM_001198536.2 link	c.1386_1387insACT		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.836_837insACT		3_prime_UTR_variant	Exon 10 of 10	1	NM_000243.3	ENSP00000219596.1		O15553-2

Frequencies

GnomAD3 genomes

AF:

0.594

AC:

87059

AN:

146534

Hom.:

26080

Cov.:

show subpopulations

Gnomad AFR

AF:

0.663

Gnomad AMI

AF:

0.439

Gnomad AMR

AF:

0.633

Gnomad ASJ

AF:

0.564

Gnomad EAS

AF:

0.611

Gnomad SAS

AF:

0.729

Gnomad FIN

AF:

0.561

Gnomad MID

AF:

0.535

Gnomad NFE

AF:

0.544

Gnomad OTH

AF:

0.586

GnomAD2 exomes

AF:

0.634

AC:

161

AN:

254

AF XY:

0.660

show subpopulations

Gnomad AFR exome

AF:

1.00

Gnomad AMR exome

AF:

0.758

Gnomad ASJ exome

AF:

0.500

Gnomad EAS exome

AF:

1.00

Gnomad FIN exome

AF:

0.500

Gnomad NFE exome

AF:

0.474

Gnomad OTH exome

AF:

0.500

GnomAD4 exome

AF:

0.577

AC:

3787

AN:

6560

Hom.:

1257

Cov.:

AF XY:

0.601

AC XY:

2676

AN XY:

4452

show subpopulations

African (AFR)

AF:

0.750

AC:

AN:

American (AMR)

AF:

0.728

AC:

AN:

136

Ashkenazi Jewish (ASJ)

AF:

0.511

AC:

AN:

East Asian (EAS)

AF:

0.786

AC:

AN:

South Asian (SAS)

AF:

0.675

AC:

2071

AN:

3070

European-Finnish (FIN)

AF:

0.493

AC:

218

AN:

442

Middle Eastern (MID)

AF:

0.438

AC:

AN:

European-Non Finnish (NFE)

AF:

0.478

AC:

1222

AN:

2554

Other (OTH)

AF:

0.431

AC:

AN:

202

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.526

Heterozygous variant carriers

124

186

248

310

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.594

AC:

87157

AN:

146650

Hom.:

26119

Cov.:

AF XY:

0.598

AC XY:

42560

AN XY:

71148

show subpopulations

African (AFR)

AF:

0.664

AC:

26066

AN:

39278

American (AMR)

AF:

0.633

AC:

9300

AN:

14684

Ashkenazi Jewish (ASJ)

AF:

0.564

AC:

1938

AN:

3434

East Asian (EAS)

AF:

0.611

AC:

2961

AN:

4850

South Asian (SAS)

AF:

0.727

AC:

3376

AN:

4642

European-Finnish (FIN)

AF:

0.561

AC:

5337

AN:

9508

Middle Eastern (MID)

AF:

0.520

AC:

153

AN:

294

European-Non Finnish (NFE)

AF:

0.544

AC:

36432

AN:

67020

Other (OTH)

AF:

0.588

AC:

1200

AN:

2042

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1633

3266

4899

6532

8165

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.353

Hom.:

581

Asia WGS

AF:

0.692

AC:

2406

AN:

3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Familial Mediterranean fever

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.35

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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chr16-3242304-C-CAGT

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