chr16-3243008-C-T

Variant names:

• chr16-3243008-C-T
• rs2075849
• NM_000243.3:c.*133G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000243.3(MEFV):​c.*133G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0187 in 1,027,446 control chromosomes in the GnomAD database, including 1,930 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.020 (311 hom., cov: 32)
  • Exomes 𝑓: 0.018 (1619 hom.)
• Consequence: MEFV NM_000243.3 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.191

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

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 16-3243008-C-T is Benign according to our data. Variant chr16-3243008-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 224066.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-3243008-C-T is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEFV	NM_000243.3	c.*133G>A		3_prime_UTR_variant	Exon 10 of 10	ENST00000219596.6	NP_000234.1
MEFV	NM_001198536.2	c.*683G>A		3_prime_UTR_variant	Exon 9 of 9		NP_001185465.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEFV	ENST00000219596.6	c.*133G>A		3_prime_UTR_variant	Exon 10 of 10	1	NM_000243.3	ENSP00000219596.1

Frequencies

GnomAD3 genomes AF: 0.0199 AC: 3033 AN: 152098 Hom.: 312 Cov.: 32

Gnomad AFR AF: 0.00198

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0215

Gnomad ASJ AF: 0.00519

Gnomad EAS AF: 0.326

Gnomad SAS AF: 0.0257

Gnomad FIN AF: 0.0591

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00194

Gnomad OTH AF: 0.0172

GnomAD4 exome AF: 0.0185 AC: 16172 AN: 875230 Hom.: 1619 Cov.: 12 AF XY: 0.0180 AC XY: 8107 AN XY: 449586

African (AFR) AF: 0.00137 AC: 30 AN: 21910

American (AMR) AF: 0.0446 AC: 1545 AN: 34678

Ashkenazi Jewish (ASJ) AF: 0.00355 AC: 73 AN: 20592

East Asian (EAS) AF: 0.284 AC: 9574 AN: 33656

South Asian (SAS) AF: 0.0149 AC: 992 AN: 66536

European-Finnish (FIN) AF: 0.0543 AC: 2110 AN: 38868

Middle Eastern (MID) AF: 0.00395 AC: 12 AN: 3040

European-Non Finnish (NFE) AF: 0.00116 AC: 713 AN: 614878

Other (OTH) AF: 0.0273 AC: 1123 AN: 41072

GnomAD4 genome AF: 0.0200 AC: 3038 AN: 152216 Hom.: 311 Cov.: 32 AF XY: 0.0241 AC XY: 1795 AN XY: 74412

African (AFR) AF: 0.00197 AC: 82 AN: 41550

American (AMR) AF: 0.0217 AC: 332 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00519 AC: 18 AN: 3466

East Asian (EAS) AF: 0.327 AC: 1685 AN: 5152

South Asian (SAS) AF: 0.0255 AC: 123 AN: 4816

European-Finnish (FIN) AF: 0.0591 AC: 627 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00194 AC: 132 AN: 68024

Other (OTH) AF: 0.0185 AC: 39 AN: 2112

Alfa AF: 0.00567 Hom.: 63

Bravo AF: 0.0198

Asia WGS AF: 0.167 AC: 578 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Familial Mediterranean fever Benign:3

Jan 25, 2016

Atomic Energy Commission of Syria (AECS)

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: case-control

- -

Feb 08, 2023

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

not provided Benign:2

Sep 07, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Acute febrile neutrophilic dermatosis Benign:1

Feb 08, 2023

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Familial Mediterranean fever, autosomal dominant Benign:1

Feb 08, 2023

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.2
DANN	Benign	0.64
PhyloP100		-0.19
Mutation Taster		=100/0	polymorphism (auto)

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

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Other links and lift over

dbSNP: rs2075849; hg19: chr16-3293008; COSMIC: COSV99560166; COSMIC: COSV99560166;