16-3253310-T-C

Variant names:

• chr16-3253310-T-C
• rs182674
• NM_000243.3:c.910+848A>G

Variant summary

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

The NM_000243.3(MEFV):​c.910+848A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.572 in 151,720 control chromosomes in the GnomAD database, including 25,928 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 0.57 (25928 hom., cov: 30)
• Consequence: MEFV NM_000243.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.987
• Publications: 6 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.75 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEFV	NM_000243.3	MANE Select	c.910+848A>G		intron	N/A	NP_000234.1
	MEFV	NM_001198536.2		c.277+3001A>G		intron	N/A	NP_001185465.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEFV	ENST00000219596.6	TSL:1 MANE Select	c.910+848A>G		intron	N/A	ENSP00000219596.1
	MEFV	ENST00000541159.5	TSL:1	c.277+3001A>G		intron	N/A	ENSP00000438711.1
	MEFV	ENST00000539145.5	TSL:1	n.277+3001A>G		intron	N/A	ENSP00000444471.1

Frequencies

GnomAD3 genomes AF: 0.571 AC: 86624 AN: 151602 Hom.: 25878 Cov.: 30

Gnomad AFR AF: 0.756

Gnomad AMI AF: 0.403

Gnomad AMR AF: 0.601

Gnomad ASJ AF: 0.452

Gnomad EAS AF: 0.451

Gnomad SAS AF: 0.488

Gnomad FIN AF: 0.516

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.486

Gnomad OTH AF: 0.540

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

GnomAD4 genome AF: 0.572 AC: 86736 AN: 151720 Hom.: 25928 Cov.: 30 AF XY: 0.572 AC XY: 42362 AN XY: 74120

African (AFR) AF: 0.757 AC: 31290 AN: 41354

American (AMR) AF: 0.601 AC: 9142 AN: 15212

Ashkenazi Jewish (ASJ) AF: 0.452 AC: 1565 AN: 3466

East Asian (EAS) AF: 0.451 AC: 2322 AN: 5146

South Asian (SAS) AF: 0.488 AC: 2346 AN: 4812

European-Finnish (FIN) AF: 0.516 AC: 5414 AN: 10490

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.486 AC: 33047 AN: 67932

Other (OTH) AF: 0.538 AC: 1133 AN: 2104

Alfa AF: 0.534 Hom.: 8578

Bravo AF: 0.587

Asia WGS AF: 0.466 AC: 1624 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.0
DANN	Benign	0.21
PhyloP100		-0.99
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: rs182674; hg19: chr16-3303310;