Genetic Variant MEFV:c.*1056G>T (chr16-3242085-C-A) – ACMG Classification: Benign (-20 pts)

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.*1056G>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 0.596 in 155,548 control chromosomes in the GnomAD database, including 27,975 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.60 ( 27251 hom., cov: 32)

Exomes 𝑓: 0.62 ( 724 hom. )

Consequence

MEFV
NM_000243.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.54

Publications

7 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, SD, AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Myriad Women’s Health, ClinGen, Orphanet
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=-0.98).

BP6

Variant 16-3242085-C-A is Benign according to our data. Variant chr16-3242085-C-A is described in ClinVar as Benign. ClinVar VariationId is 319086.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.708 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000243.3. 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.*1056G>T		3_prime_UTR	Exon 10 of 10	NP_000234.1	O15553-2
	MEFV	NM_001198536.2		c.*1606G>T		3_prime_UTR	Exon 9 of 9	NP_001185465.2	O15553-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MEFV	ENST00000219596.6	TSL:1 MANE Select	c.*1056G>T	3_prime_UTR	Exon 10 of 10	ENSP00000219596.1	O15553-2
MEFV	ENST00000956137.1		c.*1056G>T	3_prime_UTR	Exon 10 of 10	ENSP00000626196.1
MEFV	ENST00000339854.8	TSL:5	c.*1056G>T	3_prime_UTR	Exon 10 of 10	ENSP00000339639.4	F8W6Z2

Frequencies

GnomAD3 genomes

AF:

0.596

AC:

90418

AN:

151806

Hom.:

27210

Cov.:

show subpopulations

Gnomad AFR

AF:

0.663

Gnomad AMI

AF:

0.445

Gnomad AMR

AF:

0.632

Gnomad ASJ

AF:

0.565

Gnomad EAS

AF:

0.614

Gnomad SAS

AF:

0.729

Gnomad FIN

AF:

0.560

Gnomad MID

AF:

0.535

Gnomad NFE

AF:

0.545

Gnomad OTH

AF:

0.585

GnomAD4 exome

AF:

0.615

AC:

2230

AN:

3624

Hom.:

724

Cov.:

AF XY:

0.634

AC XY:

1537

AN XY:

2424

show subpopulations

African (AFR)

AF:

0.813

AC:

AN:

American (AMR)

AF:

0.661

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AF:

0.696

AC:

1230

AN:

1768

European-Finnish (FIN)

AF:

0.558

AC:

115

AN:

206

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.528

AC:

748

AN:

1418

Other (OTH)

AF:

0.557

AC:

AN:

106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.518

Heterozygous variant carriers

112

149

186

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:

0.596

AC:

90519

AN:

151924

Hom.:

27251

Cov.:

AF XY:

0.600

AC XY:

44508

AN XY:

74230

show subpopulations

African (AFR)

AF:

0.664

AC:

27494

AN:

41424

American (AMR)

AF:

0.632

AC:

9650

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.565

AC:

1960

AN:

3468

East Asian (EAS)

AF:

0.614

AC:

3162

AN:

5152

South Asian (SAS)

AF:

0.728

AC:

3510

AN:

4824

European-Finnish (FIN)

AF:

0.560

AC:

5912

AN:

10550

Middle Eastern (MID)

AF:

0.520

AC:

153

AN:

294

European-Non Finnish (NFE)

AF:

0.545

AC:

37041

AN:

67942

Other (OTH)

AF:

0.586

AC:

1232

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1867

3733

5600

7466

9333

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

764

1528

2292

3056

3820

<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:

0.491

Hom.:

2784

Bravo

AF:

0.604

Asia WGS

AF:

0.693

AC:

2410

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Familial Mediterranean fever (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

0.69

(source)

DANN

Benign

0.25

PhyloP100

-1.5

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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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