16-3251360-A-G

Variant names:

• chr16-3251360-A-G
• rs224215
• NM_000243.3:c.911-1580T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000243.3(MEFV):​c.911-1580T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 151,970 control chromosomes in the GnomAD database, including 8,799 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.32 (8799 hom., cov: 31)
• Consequence: MEFV NM_000243.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.940
• Publications: 17 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.398 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.911-1580T>C		intron	N/A	NP_000234.1	O15553-2
	MEFV	NM_001198536.2		c.278-1580T>C		intron	N/A	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.911-1580T>C		intron	N/A	ENSP00000219596.1	O15553-2
	MEFV	ENST00000541159.5	TSL:1	c.278-1580T>C		intron	N/A	ENSP00000438711.1	O15553-3
	MEFV	ENST00000539145.5	TSL:1	n.278-4114T>C		intron	N/A	ENSP00000444471.1	D2DTW1

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48892 AN: 151852 Hom.: 8806 Cov.: 31

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.256

Gnomad AMR AF: 0.406

Gnomad ASJ AF: 0.332

Gnomad EAS AF: 0.0121

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.456

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.382

Gnomad OTH AF: 0.338

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.322 AC: 48905 AN: 151970 Hom.: 8799 Cov.: 31 AF XY: 0.323 AC XY: 24013 AN XY: 74276

African (AFR) AF: 0.215 AC: 8911 AN: 41448

American (AMR) AF: 0.406 AC: 6190 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.332 AC: 1150 AN: 3468

East Asian (EAS) AF: 0.0120 AC: 62 AN: 5178

South Asian (SAS) AF: 0.164 AC: 792 AN: 4824

European-Finnish (FIN) AF: 0.456 AC: 4811 AN: 10546

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.382 AC: 25965 AN: 67952

Other (OTH) AF: 0.332 AC: 699 AN: 2104

Alfa AF: 0.361 Hom.: 33341

Bravo AF: 0.318

Asia WGS AF: 0.102 AC: 358 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.60
DANN	Benign	0.40
PhyloP100		-0.94
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: rs224215; hg19: chr16-3301360;