chr16-3255732-T-C

Variant names:

• chr16-3255732-T-C
• rs224226
• NM_000243.3:c.277+579A>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.277+579A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.525 in 151,900 control chromosomes in the GnomAD database, including 22,364 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 0.53 (22364 hom., cov: 31)
• Consequence: MEFV NM_000243.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.179
• 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=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.684 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEFV	NM_000243.3	c.277+579A>G		intron_variant	Intron 1 of 9	ENST00000219596.6	NP_000234.1
MEFV	NM_001198536.2	c.277+579A>G		intron_variant	Intron 1 of 8		NP_001185465.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEFV	ENST00000219596.6	c.277+579A>G		intron_variant	Intron 1 of 9	1	NM_000243.3	ENSP00000219596.1

Frequencies

GnomAD3 genomes AF: 0.525 AC: 79650 AN: 151782 Hom.: 22325 Cov.: 31

Gnomad AFR AF: 0.690

Gnomad AMI AF: 0.413

Gnomad AMR AF: 0.575

Gnomad ASJ AF: 0.398

Gnomad EAS AF: 0.153

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.514

Gnomad MID AF: 0.315

Gnomad NFE AF: 0.476

Gnomad OTH AF: 0.503

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

GnomAD4 genome AF: 0.525 AC: 79749 AN: 151900 Hom.: 22364 Cov.: 31 AF XY: 0.520 AC XY: 38598 AN XY: 74226

African (AFR) AF: 0.690 AC: 28614 AN: 41444

American (AMR) AF: 0.575 AC: 8762 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.398 AC: 1380 AN: 3468

East Asian (EAS) AF: 0.153 AC: 788 AN: 5142

South Asian (SAS) AF: 0.194 AC: 935 AN: 4814

European-Finnish (FIN) AF: 0.514 AC: 5420 AN: 10540

Middle Eastern (MID) AF: 0.315 AC: 92 AN: 292

European-Non Finnish (NFE) AF: 0.476 AC: 32324 AN: 67932

Other (OTH) AF: 0.501 AC: 1060 AN: 2114

Alfa AF: 0.519 Hom.: 4726

Bravo AF: 0.542

Asia WGS AF: 0.239 AC: 835 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.8
DANN	Benign	0.65
PhyloP100		0.18
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: rs224226; hg19: chr16-3305732;