rs79662406

Variant names:

• chr16-3243896-C-A
• rs79662406
• ENST00000541159.5:c.1298G>T

Your query was ambiguous. Multiple possible variants found:

• chr16-3243896-C-A
• chr16-3243896-C-G
• chr16-3243896-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001198536.2(MEFV):​c.1298G>T​(p.Arg433Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,664 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R433H) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MEFV NM_001198536.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.383
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18076536).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001198536.2. 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.1760-4G>T		splice_region intron	N/A	NP_000234.1	O15553-2
	MEFV	NM_001198536.2		c.1298G>T	p.Arg433Leu	missense	Exon 8 of 9	NP_001185465.2	O15553-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEFV	ENST00000541159.5	TSL:1	c.1298G>T	p.Arg433Leu	missense	Exon 8 of 9	ENSP00000438711.1	O15553-3
	MEFV	ENST00000219596.6	TSL:1 MANE Select	c.1760-4G>T		splice_region intron	N/A	ENSP00000219596.1	O15553-2
	MEFV	ENST00000539145.5	TSL:1	n.*393-4G>T		splice_region intron	N/A	ENSP00000444471.1	D2DTW1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461664 Hom.: 0 Cov.: 57 AF XY: 0.00000138 AC XY: 1 AN XY: 727110

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53270

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111984

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	2.4
DANN	Benign	0.94
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.38
PROVEAN	Benign	0.48	N
REVEL	Benign	0.059
Sift	Benign	0.20	T
Sift4G	Benign	0.26	T
Vest4		0.27
MutPred		0.65		Loss of methylation at R433 (P = 0.0465)
MVP		0.61
ClinPred		0.053	T
GERP RS		-1.8

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: rs79662406; hg19: chr16-3293896;