rs886051967

Variant names:

• chr16-3242379-AG-A
• rs886051967
• NM_000243.3:c.*761delC

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000243.3(MEFV):​c.*761delC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000212 in 141,220 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000021 (0 hom., cov: 24)
  • Exomes 𝑓: 0.0 (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: -1.64
• Publications: 0 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: SD, AR, AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Myriad Women’s Health, Orphanet
• familial Mediterranean fever, autosomal dominant

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.*761delC		3_prime_UTR	Exon 10 of 10	NP_000234.1	O15553-2
	MEFV	NM_001198536.2		c.*1311delC		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.*761delC		3_prime_UTR	Exon 10 of 10	ENSP00000219596.1	O15553-2
	MEFV	ENST00000956137.1		c.*761delC		3_prime_UTR	Exon 10 of 10	ENSP00000626196.1
	MEFV	ENST00000339854.8	TSL:5	c.*761delC		3_prime_UTR	Exon 10 of 10	ENSP00000339639.4	F8W6Z2

Frequencies

GnomAD3 genomes AF: 0.0000213 AC: 3 AN: 141124 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.0000557

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000151

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1108 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 752

African (AFR) AF: 0.00 AC: 0 AN: 4

American (AMR) AF: 0.00 AC: 0 AN: 12

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10

East Asian (EAS) AF: 0.00 AC: 0 AN: 20

South Asian (SAS) AF: 0.00 AC: 0 AN: 432

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 62

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 542

Other (OTH) AF: 0.00 AC: 0 AN: 22

GnomAD4 genome AF: 0.0000212 AC: 3 AN: 141220 Hom.: 0 Cov.: 24 AF XY: 0.0000290 AC XY: 2 AN XY: 68988

African (AFR) AF: 0.0000556 AC: 2 AN: 35996

American (AMR) AF: 0.00 AC: 0 AN: 14148

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3344

East Asian (EAS) AF: 0.00 AC: 0 AN: 4610

South Asian (SAS) AF: 0.00 AC: 0 AN: 4506

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9422

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 270

European-Non Finnish (NFE) AF: 0.0000151 AC: 1 AN: 66094

Other (OTH) AF: 0.00 AC: 0 AN: 1950

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Familial Mediterranean fever (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.6

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: rs886051967; hg19: chr16-3292379;