16-3243008-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
• Publications: 3 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: 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 Benign/Likely_benign. ClinVar VariationId is 224066.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000243.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEFV	NM_000243.3	MANE Select	c.*133G>A		3_prime_UTR	Exon 10 of 10	NP_000234.1
	MEFV	NM_001198536.2		c.*683G>A		3_prime_UTR	Exon 9 of 9	NP_001185465.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEFV	ENST00000219596.6	TSL:1 MANE Select	c.*133G>A		3_prime_UTR	Exon 10 of 10	ENSP00000219596.1
	MEFV	ENST00000956137.1		c.*133G>A		3_prime_UTR	Exon 10 of 10	ENSP00000626196.1
	MEFV	ENST00000339854.8	TSL:5	c.*133G>A		3_prime_UTR	Exon 10 of 10	ENSP00000339639.4

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

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Familial Mediterranean fever (3)
-	-	2	not provided (2)
-	-	1	Acute febrile neutrophilic dermatosis (1)
-	-	1	Familial Mediterranean fever, autosomal dominant (1)

Computational scores

Source: dbNSFP v4.9

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

Other links and lift over

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