rs450021

chr16-3242085-C-Achr16-3242085-C-Gchr16-3242085-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000243.3(MEFV):c.*1056G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.596 in 155,548 control chromosomes in the GnomAD database, including 27,975 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.60 (27251 hom., cov: 32)
  • Exomes 𝑓: 0.62 (724 hom.)
• Consequence: MEFV NM_000243.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.54

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 16-3242085-C-A is Benign according to our data. Variant chr16-3242085-C-A is described in ClinVar as [Benign]. Clinvar id is 319086.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.708 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MEFV	NM_000243.3	c.*1056G>T		3_prime_UTR_variant	10/10	ENST00000219596.6
MEFV	NM_001198536.2	c.*1606G>T		3_prime_UTR_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MEFV	ENST00000219596.6	c.*1056G>T		3_prime_UTR_variant	10/10	1	NM_000243.3	P3

Frequencies

GnomAD3 genomes AF: 0.596 AC: 90418 AN: 151806 Hom.: 27210 Cov.: 32

Gnomad AFR AF: 0.663

Gnomad AMI AF: 0.445

Gnomad AMR AF: 0.632

Gnomad ASJ AF: 0.565

Gnomad EAS AF: 0.614

Gnomad SAS AF: 0.729

Gnomad FIN AF: 0.560

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.545

Gnomad OTH AF: 0.585

GnomAD4 exome AF: 0.615 AC: 2230 AN: 3624 Hom.: 724 Cov.: 0 AF XY: 0.634 AC XY: 1537 AN XY: 2424

Gnomad4 AFR exome AF: 0.813

Gnomad4 AMR exome AF: 0.661

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.696

Gnomad4 FIN exome AF: 0.558

Gnomad4 NFE exome AF: 0.528

Gnomad4 OTH exome AF: 0.557

GnomAD4 genome AF: 0.596 AC: 90519 AN: 151924 Hom.: 27251 Cov.: 32 AF XY: 0.600 AC XY: 44508 AN XY: 74230

Gnomad4 AFR AF: 0.664

Gnomad4 AMR AF: 0.632

Gnomad4 ASJ AF: 0.565

Gnomad4 EAS AF: 0.614

Gnomad4 SAS AF: 0.728

Gnomad4 FIN AF: 0.560

Gnomad4 NFE AF: 0.545

Gnomad4 OTH AF: 0.586

Alfa AF: 0.491 Hom.: 2784

Bravo AF: 0.604

Asia WGS AF: 0.693 AC: 2410 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Familial Mediterranean fever Benign:1

Benign, 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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.69
Dann	Benign	0.25

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: rs450021; hg19: chr16-3292085;