rs224213

Variant names:

• chr16-3249749-G-A
• rs224213
• NM_000243.3:c.942C>T

Your query was ambiguous. Multiple possible variants found:

• chr16-3249749-G-A
• chr16-3249749-G-C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000243.3(MEFV):​c.942C>T​(p.Arg314Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.581 in 1,613,414 control chromosomes in the GnomAD database, including 276,500 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.62 (29459 hom., cov: 32)
  • Exomes 𝑓: 0.58 (247041 hom.)
• Consequence: MEFV NM_000243.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts U:1 B:15
• Conservation: PhyloP100: -1.73
• Publications: 34 publications found

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)

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 16-3249749-G-A is Benign according to our data. Variant chr16-3249749-G-A is described in ClinVar as Benign. ClinVar VariationId is 36515.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.73 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.723 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.942C>T	p.Arg314Arg	synonymous	Exon 3 of 10	NP_000234.1	O15553-2
	MEFV	NM_001198536.2		c.309C>T	p.Arg103Arg	synonymous	Exon 2 of 9	NP_001185465.2	O15553-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEFV	ENST00000219596.6	TSL:1 MANE Select	c.942C>T	p.Arg314Arg	synonymous	Exon 3 of 10	ENSP00000219596.1	O15553-2
	MEFV	ENST00000541159.5	TSL:1	c.309C>T	p.Arg103Arg	synonymous	Exon 2 of 9	ENSP00000438711.1	O15553-3
	MEFV	ENST00000539145.5	TSL:1	n.278-2503C>T		intron	N/A	ENSP00000444471.1	D2DTW1

Frequencies

GnomAD3 genomes AF: 0.616 AC: 93658 AN: 151924 Hom.: 29416 Cov.: 32

Gnomad AFR AF: 0.711

Gnomad AMI AF: 0.430

Gnomad AMR AF: 0.649

Gnomad ASJ AF: 0.585

Gnomad EAS AF: 0.707

Gnomad SAS AF: 0.744

Gnomad FIN AF: 0.570

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.548

Gnomad OTH AF: 0.601

GnomAD2 exomes AF: 0.628 AC: 155507 AN: 247588 AF XY: 0.622

Gnomad AFR exome AF: 0.712

Gnomad AMR exome AF: 0.748

Gnomad ASJ exome AF: 0.573

Gnomad EAS exome AF: 0.720

Gnomad FIN exome AF: 0.584

Gnomad NFE exome AF: 0.548

Gnomad OTH exome AF: 0.584

GnomAD4 exome AF: 0.577 AC: 843633 AN: 1461372 Hom.: 247041 Cov.: 60 AF XY: 0.580 AC XY: 421488 AN XY: 726982

African (AFR) AF: 0.718 AC: 24018 AN: 33474

American (AMR) AF: 0.737 AC: 32917 AN: 44660

Ashkenazi Jewish (ASJ) AF: 0.579 AC: 15125 AN: 26122

East Asian (EAS) AF: 0.696 AC: 27636 AN: 39684

South Asian (SAS) AF: 0.728 AC: 62777 AN: 86238

European-Finnish (FIN) AF: 0.576 AC: 30772 AN: 53392

Middle Eastern (MID) AF: 0.572 AC: 3297 AN: 5768

European-Non Finnish (NFE) AF: 0.550 AC: 611300 AN: 1111658

Other (OTH) AF: 0.593 AC: 35791 AN: 60376

GnomAD4 genome AF: 0.617 AC: 93764 AN: 152042 Hom.: 29459 Cov.: 32 AF XY: 0.622 AC XY: 46237 AN XY: 74316

African (AFR) AF: 0.712 AC: 29521 AN: 41488

American (AMR) AF: 0.650 AC: 9923 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.585 AC: 2030 AN: 3470

East Asian (EAS) AF: 0.706 AC: 3652 AN: 5170

South Asian (SAS) AF: 0.743 AC: 3581 AN: 4820

European-Finnish (FIN) AF: 0.570 AC: 6021 AN: 10560

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.548 AC: 37213 AN: 67948

Other (OTH) AF: 0.602 AC: 1271 AN: 2110

Alfa AF: 0.576 Hom.: 94533

Bravo AF: 0.626

Asia WGS AF: 0.745 AC: 2593 AN: 3478

EpiCase AF: 0.543

EpiControl AF: 0.539

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	Familial Mediterranean fever (5)
-	1	3	not provided (4)
-	-	4	not specified (4)
-	-	1	Autoinflammatory syndrome (1)
-	-	1	Familial Mediterranean fever, autosomal dominant (1)
-	-	1	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.15
DANN	Benign	0.47
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs224213; hg19: chr16-3299749; COSMIC: COSV54818607; COSMIC: COSV54818607;