rs182674

Positions:

• chr16-3253310-T-C
• chr16-3253310-T-G

Variant summary

Our verdict is Benign. Variant got -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

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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.75 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MEFV	NM_000243.3	c.910+848A>G		intron_variant		ENST00000219596.6	NP_000234.1
MEFV	NM_001198536.2	c.277+3001A>G		intron_variant			NP_001185465.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MEFV	ENST00000219596.6	c.910+848A>G		intron_variant		1	NM_000243.3	ENSP00000219596.1

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

Gnomad4 AFR AF: 0.757

Gnomad4 AMR AF: 0.601

Gnomad4 ASJ AF: 0.452

Gnomad4 EAS AF: 0.451

Gnomad4 SAS AF: 0.488

Gnomad4 FIN AF: 0.516

Gnomad4 NFE AF: 0.486

Gnomad4 OTH AF: 0.538

Alfa AF: 0.538 Hom.: 5003

Bravo AF: 0.587

Asia WGS AF: 0.466 AC: 1624 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.0
DANN	Benign	0.21

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: rs182674; hg19: chr16-3303310;