rs11466048

Variant names:

• chr16-3243132-G-A
• rs11466048
• NM_000243.3:c.*9C>T

Your query was ambiguous. Multiple possible variants found:

• chr16-3243132-G-A
• chr16-3243132-G-C
• chr16-3243132-G-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BS1 BS2

The NM_000243.3(MEFV):​c.*9C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00131 in 1,612,458 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0067 (7 hom., cov: 32)
  • Exomes 𝑓: 0.00075 (9 hom.)
• Consequence: MEFV NM_000243.3 3_prime_UTR
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:9
• Conservation: PhyloP100: -0.405
• Publications: 2 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 16-3243132-G-A is Benign according to our data. Variant chr16-3243132-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 445530.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00667 (1016/152302) while in subpopulation AFR AF = 0.0218 (904/41556). AF 95% confidence interval is 0.0206. There are 7 homozygotes in GnomAd4. There are 485 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 7 AR,AD,SD gene

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEFV	NM_000243.3	MANE Select	c.*9C>T		3_prime_UTR	Exon 10 of 10	NP_000234.1
	MEFV	NM_001198536.2		c.*559C>T		3_prime_UTR	Exon 9 of 9	NP_001185465.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEFV	ENST00000219596.6	TSL:1 MANE Select	c.*9C>T		3_prime_UTR	Exon 10 of 10	ENSP00000219596.1
	MEFV	ENST00000956137.1		c.*9C>T		3_prime_UTR	Exon 10 of 10	ENSP00000626196.1
	MEFV	ENST00000339854.8	TSL:5	c.*9C>T		3_prime_UTR	Exon 10 of 10	ENSP00000339639.4

Frequencies

GnomAD3 genomes AF: 0.00666 AC: 1013 AN: 152184 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.0217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00570

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000771

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00669

GnomAD2 exomes AF: 0.00203 AC: 511 AN: 251240 AF XY: 0.00154

Gnomad AFR exome AF: 0.0248

Gnomad AMR exome AF: 0.00234

Gnomad ASJ exome AF: 0.0000993

Gnomad EAS exome AF: 0.000272

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000123

Gnomad OTH exome AF: 0.000978

GnomAD4 exome AF: 0.000753 AC: 1100 AN: 1460156 Hom.: 9 Cov.: 31 AF XY: 0.000677 AC XY: 492 AN XY: 726410

African (AFR) AF: 0.0224 AC: 748 AN: 33436

American (AMR) AF: 0.00241 AC: 108 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26132

East Asian (EAS) AF: 0.00136 AC: 54 AN: 39698

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86188

European-Finnish (FIN) AF: 0.0000188 AC: 1 AN: 53332

Middle Eastern (MID) AF: 0.00206 AC: 10 AN: 4854

European-Non Finnish (NFE) AF: 0.0000576 AC: 64 AN: 1111528

Other (OTH) AF: 0.00186 AC: 112 AN: 60264

GnomAD4 genome AF: 0.00667 AC: 1016 AN: 152302 Hom.: 7 Cov.: 32 AF XY: 0.00651 AC XY: 485 AN XY: 74470

African (AFR) AF: 0.0218 AC: 904 AN: 41556

American (AMR) AF: 0.00569 AC: 87 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3468

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5178

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

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

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68036

Other (OTH) AF: 0.00662 AC: 14 AN: 2116

Alfa AF: 0.00287 Hom.: 3

Bravo AF: 0.00771

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	1	2	Familial Mediterranean fever (3)
-	-	1	Autoinflammatory syndrome (1)
-	-	1	MEFV-related disorder (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.4
DANN	Benign	0.42
PhyloP100		-0.41
Mutation Taster		=100/0	polymorphism

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: rs11466048; hg19: chr16-3293132;