chr16-3243888-C-G

Variant names:

• chr16-3243888-C-G
• rs1231122
• ENST00000541159.5:c.1306G>C

Variant summary

Our verdict is Likely benign. The variant received -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. 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Benign in ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: MEFV ENST00000541159.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.206
• Publications: 41 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: Likely_benign. The variant received -2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000541159.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEFV	NM_000243.3	MANE Select	c.1764G>C	p.Pro588Pro	synonymous	Exon 9 of 10	NP_000234.1
	MEFV	NM_001198536.2		c.1306G>C	p.Gly436Arg	missense	Exon 8 of 9	NP_001185465.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEFV	ENST00000541159.5	TSL:1	c.1306G>C	p.Gly436Arg	missense	Exon 8 of 9	ENSP00000438711.1
	MEFV	ENST00000219596.6	TSL:1 MANE Select	c.1764G>C	p.Pro588Pro	synonymous	Exon 9 of 10	ENSP00000219596.1
	MEFV	ENST00000539145.5	TSL:1	n.*397G>C		non_coding_transcript_exon	Exon 6 of 7	ENSP00000444471.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 57

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 40777

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
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
PhyloP100		-0.21
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

Other links and lift over

dbSNP: rs1231122; hg19: chr16-3293888;