16-3243888-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000541159.5(MEFV):c.1306G>C(p.Gly436Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/15 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 nucleotide change resulting in same amino acid change has been previously reported as Benignin ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: MEFV ENST00000541159.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.206

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.047345877).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MEFV	NM_000243.3	c.1764G>C	p.Pro588=	synonymous_variant	9/10	ENST00000219596.6
MEFV	NM_001198536.2	c.1306G>C	p.Gly436Arg	missense_variant	8/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MEFV	ENST00000219596.6	c.1764G>C	p.Pro588=	synonymous_variant	9/10	1	NM_000243.3	P3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 57

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.060	T
BayesDel_noAF	Benign	-0.32
Cadd	Benign	4.8
Dann	Benign	0.23
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.051	N
LIST_S2	Benign	0.27	T
M_CAP	Benign	0.0093	T
MetaRNN	Benign	0.047	T
MetaSVM	Benign	-0.96	T
MutationTaster	Benign	1.0	P;P;P;P
PROVEAN	Benign	1.7	N
REVEL	Benign	0.053
Sift	Benign	1.0	T
Sift4G	Benign	0.76	T
Vest4		0.16
MutPred		0.30		Gain of MoRF binding (P = 0.0046);
MVP		0.40
ClinPred		0.040	T
GERP RS		-0.23

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: rs1231122; hg19: chr16-3293888;