rs224217

Positions:

• chr16-3251757-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000243.3(MEFV):​c.911-1977C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.437 in 151,982 control chromosomes in the GnomAD database, including 15,059 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 0.44 (15059 hom., cov: 31)
• Consequence: MEFV NM_000243.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0810

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.513 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MEFV	NM_000243.3	c.911-1977C>T		intron_variant		ENST00000219596.6
MEFV	NM_001198536.2	c.278-1977C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MEFV	ENST00000219596.6	c.911-1977C>T		intron_variant		1	NM_000243.3	P3

Frequencies

GnomAD3 genomes AF: 0.437 AC: 66306 AN: 151864 Hom.: 15045 Cov.: 31

Gnomad AFR AF: 0.385

Gnomad AMI AF: 0.389

Gnomad AMR AF: 0.523

Gnomad ASJ AF: 0.407

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.522

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.475

Gnomad OTH AF: 0.435

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

GnomAD4 genome AF: 0.437 AC: 66363 AN: 151982 Hom.: 15059 Cov.: 31 AF XY: 0.435 AC XY: 32270 AN XY: 74262

Gnomad4 AFR AF: 0.385

Gnomad4 AMR AF: 0.523

Gnomad4 ASJ AF: 0.407

Gnomad4 EAS AF: 0.152

Gnomad4 SAS AF: 0.227

Gnomad4 FIN AF: 0.522

Gnomad4 NFE AF: 0.475

Gnomad4 OTH AF: 0.433

Alfa AF: 0.472 Hom.: 2749

Bravo AF: 0.440

Asia WGS AF: 0.223 AC: 778 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.2
DANN	Benign	0.24

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

Publications

LitVar

Other links and lift over

dbSNP: rs224217; hg19: chr16-3301757;