rs224204

Positions:

• chr16-3246429-G-A

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.1610+96C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 1,418,208 control chromosomes in the GnomAD database, including 168,563 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.46 (16399 hom., cov: 31)
  • Exomes 𝑓: 0.49 (152164 hom.)
• Consequence: MEFV NM_000243.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.212

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 16-3246429-G-A is Benign according to our data. Variant chr16-3246429-G-A is described in ClinVar as [Benign]. Clinvar id is 439879.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-3246429-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MEFV	NM_000243.3	c.1610+96C>T		intron_variant		ENST00000219596.6	NP_000234.1
MEFV	NM_001198536.2	c.977+96C>T		intron_variant			NP_001185465.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MEFV	ENST00000219596.6	c.1610+96C>T		intron_variant		1	NM_000243.3	ENSP00000219596	P3

Frequencies

GnomAD3 genomes AF: 0.462 AC: 70117 AN: 151760 Hom.: 16382 Cov.: 31

Gnomad AFR AF: 0.382

Gnomad AMI AF: 0.376

Gnomad AMR AF: 0.538

Gnomad ASJ AF: 0.444

Gnomad EAS AF: 0.582

Gnomad SAS AF: 0.418

Gnomad FIN AF: 0.534

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.479

Gnomad OTH AF: 0.451

GnomAD4 exome AF: 0.487 AC: 617222 AN: 1266330 Hom.: 152164 Cov.: 17 AF XY: 0.484 AC XY: 309042 AN XY: 638836

Gnomad4 AFR exome AF: 0.377

Gnomad4 AMR exome AF: 0.643

Gnomad4 ASJ exome AF: 0.437

Gnomad4 EAS exome AF: 0.581

Gnomad4 SAS exome AF: 0.423

Gnomad4 FIN exome AF: 0.534

Gnomad4 NFE exome AF: 0.485

Gnomad4 OTH exome AF: 0.477

GnomAD4 genome AF: 0.462 AC: 70171 AN: 151878 Hom.: 16399 Cov.: 31 AF XY: 0.467 AC XY: 34666 AN XY: 74232

Gnomad4 AFR AF: 0.383

Gnomad4 AMR AF: 0.538

Gnomad4 ASJ AF: 0.444

Gnomad4 EAS AF: 0.582

Gnomad4 SAS AF: 0.417

Gnomad4 FIN AF: 0.534

Gnomad4 NFE AF: 0.479

Gnomad4 OTH AF: 0.449

Alfa AF: 0.468 Hom.: 5484

Bravo AF: 0.466

Asia WGS AF: 0.487 AC: 1693 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Nov 12, 2023	This variant is classified as Benign based on local population frequency. This variant was detected in 73% of patients studied by a panel of primary immunodeficiencies. Number of patients: 70. Only high quality variants are reported. -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Jul 03, 2018	- -

not provided Benign:2

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

Familial Mediterranean fever, autosomal dominant Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 01, 2021

- -

Familial Mediterranean fever Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 01, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.5
DANN	Benign	0.34

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: rs224204; hg19: chr16-3296429; COSMIC: COSV54824405;