rs224206

Variant names:

• chr16-3247073-A-G
• rs224206
• NM_000243.3:c.1530T>C

Your query was ambiguous. Multiple possible variants found:

• chr16-3247073-A-G
• chr16-3247073-A-T

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.1530T>C​(p.Asp510Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.57 in 1,613,894 control chromosomes in the GnomAD database, including 266,060 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.60 (27683 hom., cov: 32)
  • Exomes 𝑓: 0.57 (238377 hom.)
• Consequence: MEFV NM_000243.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:15
• Conservation: PhyloP100: -4.78
• Publications: 29 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):

• familial Mediterranean fever

  Inheritance: AD, AR, SD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, Myriad Women’s Health, ClinGen
• autosomal recessive familial Mediterranean fever

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
• 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=-0.97).
• BP6: Variant 16-3247073-A-G is Benign according to our data. Variant chr16-3247073-A-G is described in ClinVar as Benign. ClinVar VariationId is 36503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.78 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.707 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.1530T>C	p.Asp510Asp	synonymous	Exon 5 of 10	NP_000234.1
	MEFV	NM_001198536.2		c.897T>C	p.Asp299Asp	synonymous	Exon 4 of 9	NP_001185465.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEFV	ENST00000219596.6	TSL:1 MANE Select	c.1530T>C	p.Asp510Asp	synonymous	Exon 5 of 10	ENSP00000219596.1
	MEFV	ENST00000541159.5	TSL:1	c.897T>C	p.Asp299Asp	synonymous	Exon 4 of 9	ENSP00000438711.1
	MEFV	ENST00000539145.5	TSL:1	n.*163T>C		non_coding_transcript_exon	Exon 2 of 7	ENSP00000444471.1

Frequencies

GnomAD3 genomes AF: 0.599 AC: 90981 AN: 151926 Hom.: 27643 Cov.: 32

Gnomad AFR AF: 0.685

Gnomad AMI AF: 0.402

Gnomad AMR AF: 0.628

Gnomad ASJ AF: 0.552

Gnomad EAS AF: 0.644

Gnomad SAS AF: 0.728

Gnomad FIN AF: 0.559

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.539

Gnomad OTH AF: 0.580

GnomAD2 exomes AF: 0.612 AC: 153868 AN: 251414 AF XY: 0.606

Gnomad AFR exome AF: 0.683

Gnomad AMR exome AF: 0.740

Gnomad ASJ exome AF: 0.546

Gnomad EAS exome AF: 0.656

Gnomad FIN exome AF: 0.570

Gnomad NFE exome AF: 0.541

Gnomad OTH exome AF: 0.571

GnomAD4 exome AF: 0.568 AC: 829639 AN: 1461850 Hom.: 238377 Cov.: 73 AF XY: 0.570 AC XY: 414494 AN XY: 727228

African (AFR) AF: 0.692 AC: 23162 AN: 33480

American (AMR) AF: 0.729 AC: 32606 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.551 AC: 14393 AN: 26136

East Asian (EAS) AF: 0.638 AC: 25339 AN: 39700

South Asian (SAS) AF: 0.714 AC: 61585 AN: 86258

European-Finnish (FIN) AF: 0.563 AC: 30052 AN: 53412

Middle Eastern (MID) AF: 0.561 AC: 3236 AN: 5768

European-Non Finnish (NFE) AF: 0.544 AC: 604565 AN: 1111978

Other (OTH) AF: 0.575 AC: 34701 AN: 60394

GnomAD4 genome AF: 0.599 AC: 91082 AN: 152044 Hom.: 27683 Cov.: 32 AF XY: 0.603 AC XY: 44835 AN XY: 74328

African (AFR) AF: 0.685 AC: 28423 AN: 41472

American (AMR) AF: 0.628 AC: 9599 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.552 AC: 1915 AN: 3468

East Asian (EAS) AF: 0.644 AC: 3326 AN: 5168

South Asian (SAS) AF: 0.727 AC: 3511 AN: 4830

European-Finnish (FIN) AF: 0.559 AC: 5901 AN: 10564

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.540 AC: 36661 AN: 67952

Other (OTH) AF: 0.581 AC: 1225 AN: 2108

Alfa AF: 0.555 Hom.: 38867

Bravo AF: 0.608

Asia WGS AF: 0.703 AC: 2445 AN: 3478

EpiCase AF: 0.535

EpiControl AF: 0.531

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	Familial Mediterranean fever (5)
-	-	4	not specified (4)
-	-	3	not provided (3)
-	-	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	-0.97
CADD	Benign	0.074
DANN	Benign	0.31
PhyloP100		-4.8
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: rs224206; hg19: chr16-3297073; COSMIC: COSV54819248;