chr16-3242896-C-T

Position:

• chr16-3242896-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000243.3(MEFV):​c.*245G>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 0.583 in 542,734 control chromosomes in the GnomAD database, including 93,440 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 (26353 hom., cov: 30)
  • Exomes 𝑓: 0.58 (67087 hom.)
• Consequence: MEFV NM_000243.3 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -2.20

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 16-3242896-C-T is Benign according to our data. Variant chr16-3242896-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 224064.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-3242896-C-T is described in Lovd as [Benign].
• 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/exons	MANE	Protein	UniProt
MEFV	NM_000243.3	c.*245G>A		3_prime_UTR_variant	10/10	ENST00000219596.6	NP_000234.1
MEFV	NM_001198536.2	c.*795G>A		3_prime_UTR_variant	9/9		NP_001185465.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MEFV	ENST00000219596	c.*245G>A		3_prime_UTR_variant	10/10	1	NM_000243.3	ENSP00000219596.1

Frequencies

GnomAD3 genomes AF: 0.586 AC: 88909 AN: 151736 Hom.: 26311 Cov.: 30

Gnomad AFR AF: 0.643

Gnomad AMI AF: 0.402

Gnomad AMR AF: 0.622

Gnomad ASJ AF: 0.564

Gnomad EAS AF: 0.614

Gnomad SAS AF: 0.729

Gnomad FIN AF: 0.559

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.539

Gnomad OTH AF: 0.570

GnomAD4 exome AF: 0.581 AC: 227176 AN: 390878 Hom.: 67087 Cov.: 4 AF XY: 0.588 AC XY: 121911 AN XY: 207168

Gnomad4 AFR exome AF: 0.641

Gnomad4 AMR exome AF: 0.698

Gnomad4 ASJ exome AF: 0.562

Gnomad4 EAS exome AF: 0.618

Gnomad4 SAS exome AF: 0.710

Gnomad4 FIN exome AF: 0.560

Gnomad4 NFE exome AF: 0.544

Gnomad4 OTH exome AF: 0.572

GnomAD4 genome AF: 0.586 AC: 89010 AN: 151856 Hom.: 26353 Cov.: 30 AF XY: 0.591 AC XY: 43836 AN XY: 74188

Gnomad4 AFR AF: 0.644

Gnomad4 AMR AF: 0.623

Gnomad4 ASJ AF: 0.564

Gnomad4 EAS AF: 0.613

Gnomad4 SAS AF: 0.728

Gnomad4 FIN AF: 0.559

Gnomad4 NFE AF: 0.539

Gnomad4 OTH AF: 0.572

Alfa AF: 0.548 Hom.: 20903

Bravo AF: 0.593

Asia WGS AF: 0.691 AC: 2404 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Familial Mediterranean fever Benign:3

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Feb 08, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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. -
Likely benign, criteria provided, single submitter	case-control	Atomic Energy Commission of Syria (AECS)	Jan 25, 2016	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 26, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Acute febrile neutrophilic dermatosis Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Feb 08, 2023

- -

Familial Mediterranean fever, autosomal dominant Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Feb 08, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.38
DANN	Benign	0.51

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

Other links and lift over

dbSNP: rs2741919; hg19: chr16-3292896;