rs1231122

chr16-3243888-C-Achr16-3243888-C-Gchr16-3243888-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PVS1_Moderate PM2 BP6_Moderate

The ENST00000541159.5(MEFV):c.1306G>T(p.Gly436Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,492 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: MEFV ENST00000541159.5 stop_gained
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• 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 Uncertain_significance. Variant got 2 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0239 CDS is truncated, and there are 1 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 16-3243888-C-A is Benign according to our data. Variant chr16-3243888-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 1147321.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MEFV	NM_000243.3	c.1764G>T	p.Pro588=	synonymous_variant	9/10	ENST00000219596.6
MEFV	NM_001198536.2	c.1306G>T	p.Gly436Ter	stop_gained	8/9

Ensembl

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

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.0000279 AC: 7 AN: 250496 Hom.: 0 AF XY: 0.0000295 AC XY: 4 AN XY: 135460

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000382

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461492 Hom.: 0 Cov.: 57 AF XY: 0.00000413 AC XY: 3 AN XY: 727010

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000176

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ExAC AF: 0.0000247 AC: 3

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

Familial Mediterranean fever Benign:2

Likely benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 03, 2020	- -
Likely benign, criteria provided, single submitter	clinical testing	Invitae	Dec 30, 2023	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.73
Cadd	Benign	4.4
Dann	Benign	0.94
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.049	N
MutationTaster	Benign	0.00093	P;P;P;P
Vest4		0.35
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;