NM_000243.3:c.*245G>A

Variant names:

• chr16-3242896-C-T
• rs2741919
• NM_000243.3:c.*245G>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.*245G>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 0.583 in 542,734 control chromosomes in the GnomAD database, including 93,440 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.59 (26353 hom., cov: 30)
  • Exomes 𝑓: 0.58 (67087 hom.)
• Consequence: MEFV NM_000243.3 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -2.20
• Publications: 21 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):

• autosomal recessive familial Mediterranean fever

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
• familial Mediterranean fever

  Inheritance: AR, SD, AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Myriad Women’s Health, ClinGen, Orphanet
• 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 16-3242896-C-T is Benign according to our data. Variant chr16-3242896-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 224064.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.707 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.*245G>A		3_prime_UTR	Exon 10 of 10	NP_000234.1	O15553-2
	MEFV	NM_001198536.2		c.*795G>A		3_prime_UTR	Exon 9 of 9	NP_001185465.2	O15553-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEFV	ENST00000219596.6	TSL:1 MANE Select	c.*245G>A		3_prime_UTR	Exon 10 of 10	ENSP00000219596.1	O15553-2
	MEFV	ENST00000956137.1		c.*245G>A		3_prime_UTR	Exon 10 of 10	ENSP00000626196.1
	MEFV	ENST00000339854.8	TSL:5	c.*245G>A		3_prime_UTR	Exon 10 of 10	ENSP00000339639.4	F8W6Z2

Frequencies

GnomAD3 genomes AF: 0.586 AC: 88909 AN: 151736 Hom.: 26311 Cov.: 30

Gnomad AFR AF: 0.643

Gnomad AMI AF: 0.402

Gnomad AMR AF: 0.622

Gnomad ASJ AF: 0.564

Gnomad EAS AF: 0.614

Gnomad SAS AF: 0.729

Gnomad FIN AF: 0.559

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.539

Gnomad OTH AF: 0.570

GnomAD4 exome AF: 0.581 AC: 227176 AN: 390878 Hom.: 67087 Cov.: 4 AF XY: 0.588 AC XY: 121911 AN XY: 207168

African (AFR) AF: 0.641 AC: 7278 AN: 11358

American (AMR) AF: 0.698 AC: 12456 AN: 17856

Ashkenazi Jewish (ASJ) AF: 0.562 AC: 6722 AN: 11956

East Asian (EAS) AF: 0.618 AC: 15592 AN: 25216

South Asian (SAS) AF: 0.710 AC: 32580 AN: 45866

European-Finnish (FIN) AF: 0.560 AC: 12542 AN: 22412

Middle Eastern (MID) AF: 0.533 AC: 897 AN: 1682

European-Non Finnish (NFE) AF: 0.544 AC: 126405 AN: 232326

Other (OTH) AF: 0.572 AC: 12704 AN: 22206

GnomAD4 genome AF: 0.586 AC: 89010 AN: 151856 Hom.: 26353 Cov.: 30 AF XY: 0.591 AC XY: 43836 AN XY: 74188

African (AFR) AF: 0.644 AC: 26662 AN: 41410

American (AMR) AF: 0.623 AC: 9498 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.564 AC: 1953 AN: 3464

East Asian (EAS) AF: 0.613 AC: 3168 AN: 5166

South Asian (SAS) AF: 0.728 AC: 3504 AN: 4816

European-Finnish (FIN) AF: 0.559 AC: 5873 AN: 10498

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.539 AC: 36631 AN: 67944

Other (OTH) AF: 0.572 AC: 1207 AN: 2110

Alfa AF: 0.561 Hom.: 30456

Bravo AF: 0.593

Asia WGS AF: 0.691 AC: 2404 AN: 3478

ClinVar

ClinVar submissions

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	0.38
DANN	Benign	0.51
PhyloP100		-2.2
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: rs2741919; hg19: chr16-3292896;