Genetic Variant MEFV:c.*779delT (chr16-3242361-CA-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_000243.3(MEFV):c.*779delT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 73,234 control chromosomes in the GnomAD database, including 819 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.12 ( 819 hom., cov: 22)

Exomes 𝑓: 0.23 ( 0 hom. )

Consequence

MEFV
NM_000243.3 3_prime_UTR

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.320

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 -8 ACMG points.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.28 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEFV	NM_000243.3 link	c.*779delT		3_prime_UTR_variant	Exon 10 of 10	ENST00000219596.6	NP_000234.1	O15553-2
MEFV	NM_001198536.2 link	c.*1329delT		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.*779delT		3_prime_UTR_variant	Exon 10 of 10	1	NM_000243.3	ENSP00000219596.1		O15553-2

Frequencies

GnomAD3 genomes

AF:

0.124

AC:

9015

AN:

72992

Hom.:

820

Cov.:

show subpopulations

Gnomad AFR

AF:

0.285

Gnomad AMI

AF:

0.0542

Gnomad AMR

AF:

0.102

Gnomad ASJ

AF:

0.0968

Gnomad EAS

AF:

0.296

Gnomad SAS

AF:

0.0730

Gnomad FIN

AF:

0.0137

Gnomad MID

AF:

0.128

Gnomad NFE

AF:

0.0294

Gnomad OTH

AF:

0.122

GnomAD4 exome

AF:

0.233

AC:

AN:

232

Hom.:

Cov.:

AF XY:

0.235

AC XY:

AN XY:

162

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.333

AC:

AN:

South Asian (SAS)

AF:

0.262

AC:

AN:

130

European-Finnish (FIN)

AF:

0.250

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.190

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.416

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.124

AC:

9024

AN:

73002

Hom.:

819

Cov.:

AF XY:

0.127

AC XY:

4350

AN XY:

34180

show subpopulations

African (AFR)

AF:

0.285

AC:

5983

AN:

21022

American (AMR)

AF:

0.102

AC:

624

AN:

6100

Ashkenazi Jewish (ASJ)

AF:

0.0968

AC:

203

AN:

2098

East Asian (EAS)

AF:

0.297

AC:

846

AN:

2852

South Asian (SAS)

AF:

0.0742

AC:

171

AN:

2304

European-Finnish (FIN)

AF:

0.0137

AC:

AN:

2554

Middle Eastern (MID)

AF:

0.125

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0294

AC:

1019

AN:

34660

Other (OTH)

AF:

0.120

AC:

111

AN:

926

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

310

621

931

1242

1552

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00115

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Familial Mediterranean fever

Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.32

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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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16-3242361-CAAAAAAA-CAAAAAA

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