16-3242139-C-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000243.3(MEFV):c.*1002G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00068 (0 hom., cov: 30)
  • Exomes 𝑓: 0.00094 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MEFV NM_000243.3 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.532

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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MEFV	NM_000243.3	c.*1002G>C		3_prime_UTR_variant	10/10	ENST00000219596.6
MEFV	NM_001198536.2	c.*1552G>C		3_prime_UTR_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MEFV	ENST00000219596.6	c.*1002G>C		3_prime_UTR_variant	10/10	1	NM_000243.3	P3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 96 AN: 140542 Hom.: 0 Cov.: 30 FAILED QC

Gnomad AFR AF: 0.000826

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000705

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00329

Gnomad SAS AF: 0.000690

Gnomad FIN AF: 0.00130

Gnomad MID AF: 0.00935

Gnomad NFE AF: 0.000326

Gnomad OTH AF: 0.00106

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000940 AC: 32 AN: 34032 Hom.: 0 Cov.: 0 AF XY: 0.000977 AC XY: 21 AN XY: 21500

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00165

Gnomad4 ASJ exome AF: 0.00114

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000785

Gnomad4 FIN exome AF: 0.000442

Gnomad4 NFE exome AF: 0.00110

Gnomad4 OTH exome AF: 0.000797

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000675 AC: 95 AN: 140646 Hom.: 0 Cov.: 30 AF XY: 0.000654 AC XY: 45 AN XY: 68812

Gnomad4 AFR AF: 0.000850

Gnomad4 AMR AF: 0.000704

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00330

Gnomad4 SAS AF: 0.000461

Gnomad4 FIN AF: 0.00130

Gnomad4 NFE AF: 0.000326

Gnomad4 OTH AF: 0.000525

Alfa AF: 0.00306 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Familial Mediterranean fever Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.70
Dann	Benign	0.44

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: rs1316887692; hg19: chr16-3292139;