Genetic Variant NM_000243.3:c.*779dupT (chr16-3242361-C-CA) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1BS2

The NM_000243.3(MEFV):c.*779dupT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.03 in 73,224 control chromosomes in the GnomAD database, including 32 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.030 ( 32 hom., cov: 22)

Exomes 𝑓: 0.025 ( 0 hom. )

Consequence

MEFV
NM_000243.3 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.320

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.03 (2193/72988) while in subpopulation NFE AF= 0.0361 (1249/34634). AF 95% confidence interval is 0.0344. There are 32 homozygotes in gnomad4. There are 984 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 32 SD gene

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes

AF:

0.0301

AC:

2195

AN:

72978

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0200

Gnomad AMI

AF:

0.00985

Gnomad AMR

AF:

0.0253

Gnomad ASJ

AF:

0.0890

Gnomad EAS

AF:

0.0294

Gnomad SAS

AF:

0.0143

Gnomad FIN

AF:

0.0106

Gnomad MID

AF:

0.0349

Gnomad NFE

AF:

0.0361

Gnomad OTH

AF:

0.0370

GnomAD4 exome

AF:

0.0254

AC:

AN:

236

Hom.:

Cov.:

AF XY:

0.0361

AC XY:

AN XY:

166

show subpopulations

Gnomad4 AMR exome

AF:

0.250

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0299

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0119

GnomAD4 genome

AF:

0.0300

AC:

2193

AN:

72988

Hom.:

Cov.:

AF XY:

0.0288

AC XY:

984

AN XY:

34182

show subpopulations

Gnomad4 AFR

AF:

0.0200

Gnomad4 AMR

AF:

0.0253

Gnomad4 ASJ

AF:

0.0890

Gnomad4 EAS

AF:

0.0291

Gnomad4 SAS

AF:

0.0139

Gnomad4 FIN

AF:

0.0106

Gnomad4 NFE

AF:

0.0361

Gnomad4 OTH

AF:

0.0367

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over