16-3242361-CAAAAAAA-CAAAAA

Variant names:

• chr16-3242361-CAA-C
• rs60407399
• NM_000243.3:c.*778_*779delTT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_000243.3(MEFV):​c.*778_*779delTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00187 in 73,218 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0014 (0 hom., cov: 22)
  • Exomes 𝑓: 0.14 (0 hom.)
• Consequence: MEFV NM_000243.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.320

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 -8 ACMG points.

• BA1: GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0957 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEFV	NM_000243.3	c.*778_*779delTT		3_prime_UTR_variant	Exon 10 of 10	ENST00000219596.6	NP_000234.1
MEFV	NM_001198536.2	c.*1328_*1329delTT		3_prime_UTR_variant	Exon 9 of 9		NP_001185465.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEFV	ENST00000219596	c.*778_*779delTT		3_prime_UTR_variant	Exon 10 of 10	1	NM_000243.3	ENSP00000219596.1

Frequencies

GnomAD3 genomes AF: 0.00144 AC: 105 AN: 72978 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.00324

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00164

Gnomad ASJ AF: 0.000476

Gnomad EAS AF: 0.000701

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00235

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000520

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.139 AC: 32 AN: 230 Hom.: 0 AF XY: 0.142 AC XY: 23 AN XY: 162

Gnomad4 AMR exome AF: 0.250

Gnomad4 EAS exome AF: 0.167

Gnomad4 SAS exome AF: 0.146

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.110

GnomAD4 genome AF: 0.00144 AC: 105 AN: 72988 Hom.: 0 Cov.: 22 AF XY: 0.00146 AC XY: 50 AN XY: 34168

Gnomad4 AFR AF: 0.00323

Gnomad4 AMR AF: 0.00164

Gnomad4 ASJ AF: 0.000476

Gnomad4 EAS AF: 0.000702

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00235

Gnomad4 NFE AF: 0.000520

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs60407399; hg19: chr16-3292361;