chr16-3242874-C-T

Variant names:

• chr16-3242874-C-T
• rs2741918
• NM_000243.3:c.*267G>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.*267G>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 0.585 in 501,962 control chromosomes in the GnomAD database, including 87,421 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 (26841 hom., cov: 30)
  • Exomes 𝑓: 0.58 (60580 hom.)
• Consequence: MEFV NM_000243.3 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.0270
• Publications: 11 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=-0.86).
• BP6: Variant 16-3242874-C-T is Benign according to our data. Variant chr16-3242874-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 224065.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.*267G>A		3_prime_UTR	Exon 10 of 10	NP_000234.1	O15553-2
	MEFV	NM_001198536.2		c.*817G>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.*267G>A		3_prime_UTR	Exon 10 of 10	ENSP00000219596.1	O15553-2
	MEFV	ENST00000956137.1		c.*267G>A		3_prime_UTR	Exon 10 of 10	ENSP00000626196.1
	MEFV	ENST00000339854.8	TSL:5	c.*267G>A		3_prime_UTR	Exon 10 of 10	ENSP00000339639.4	F8W6Z2

Frequencies

GnomAD3 genomes AF: 0.591 AC: 89647 AN: 151578 Hom.: 26799 Cov.: 30

Gnomad AFR AF: 0.662

Gnomad AMI AF: 0.400

Gnomad AMR AF: 0.625

Gnomad ASJ AF: 0.564

Gnomad EAS AF: 0.615

Gnomad SAS AF: 0.728

Gnomad FIN AF: 0.560

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.539

Gnomad OTH AF: 0.576

GnomAD4 exome AF: 0.583 AC: 204090 AN: 350264 Hom.: 60580 Cov.: 3 AF XY: 0.590 AC XY: 109942 AN XY: 186302

African (AFR) AF: 0.661 AC: 6832 AN: 10336

American (AMR) AF: 0.694 AC: 10969 AN: 15814

Ashkenazi Jewish (ASJ) AF: 0.561 AC: 5945 AN: 10606

East Asian (EAS) AF: 0.618 AC: 13356 AN: 21600

South Asian (SAS) AF: 0.710 AC: 31864 AN: 44910

European-Finnish (FIN) AF: 0.560 AC: 10614 AN: 18964

Middle Eastern (MID) AF: 0.536 AC: 799 AN: 1490

European-Non Finnish (NFE) AF: 0.543 AC: 112410 AN: 206868

Other (OTH) AF: 0.574 AC: 11301 AN: 19676

GnomAD4 genome AF: 0.592 AC: 89750 AN: 151698 Hom.: 26841 Cov.: 30 AF XY: 0.596 AC XY: 44163 AN XY: 74114

African (AFR) AF: 0.663 AC: 27399 AN: 41340

American (AMR) AF: 0.625 AC: 9515 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.564 AC: 1958 AN: 3470

East Asian (EAS) AF: 0.614 AC: 3162 AN: 5148

South Asian (SAS) AF: 0.727 AC: 3497 AN: 4810

European-Finnish (FIN) AF: 0.560 AC: 5864 AN: 10474

Middle Eastern (MID) AF: 0.500 AC: 145 AN: 290

European-Non Finnish (NFE) AF: 0.539 AC: 36629 AN: 67924

Other (OTH) AF: 0.577 AC: 1218 AN: 2110

Alfa AF: 0.567 Hom.: 11555

Bravo AF: 0.600

Asia WGS AF: 0.692 AC: 2407 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	-0.86
CADD	Benign	2.6
DANN	Benign	0.47
PhyloP100		0.027
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2741918; hg19: chr16-3292874;