chr16-3242361-CA-C

Position:

• chr16-3242361-CA-C

Variant summary

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

The NM_000243.3(MEFV):​c.*779delT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 73,234 control chromosomes in the GnomAD database, including 819 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.12 (819 hom., cov: 22)
  • Exomes 𝑓: 0.23 (0 hom.)
• Consequence: MEFV NM_000243.3 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.28 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MEFV	NM_000243.3	c.*779delT		3_prime_UTR_variant	10/10	ENST00000219596.6	NP_000234.1
MEFV	NM_001198536.2	c.*1329delT		3_prime_UTR_variant	9/9		NP_001185465.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MEFV	ENST00000219596	c.*779delT		3_prime_UTR_variant	10/10	1	NM_000243.3	ENSP00000219596.1

Frequencies

GnomAD3 genomes AF: 0.124 AC: 9015 AN: 72992 Hom.: 820 Cov.: 22

Gnomad AFR AF: 0.285

Gnomad AMI AF: 0.0542

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.0968

Gnomad EAS AF: 0.296

Gnomad SAS AF: 0.0730

Gnomad FIN AF: 0.0137

Gnomad MID AF: 0.128

Gnomad NFE AF: 0.0294

Gnomad OTH AF: 0.122

GnomAD4 exome AF: 0.233 AC: 54 AN: 232 Hom.: 0 Cov.: 0 AF XY: 0.235 AC XY: 38 AN XY: 162

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 0.333

Gnomad4 SAS exome AF: 0.262

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.190

GnomAD4 genome AF: 0.124 AC: 9024 AN: 73002 Hom.: 819 Cov.: 22 AF XY: 0.127 AC XY: 4350 AN XY: 34180

Gnomad4 AFR AF: 0.285

Gnomad4 AMR AF: 0.102

Gnomad4 ASJ AF: 0.0968

Gnomad4 EAS AF: 0.297

Gnomad4 SAS AF: 0.0742

Gnomad4 FIN AF: 0.0137

Gnomad4 NFE AF: 0.0294

Gnomad4 OTH AF: 0.120

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Familial Mediterranean fever Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

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;