NM_000243.3:c.*774_*779delTTTTTT

Variant names:

• chr16-3242361-CAAAAAA-C
• rs60407399
• NM_000243.3:c.*774_*779delTTTTTT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_000243.3(MEFV):​c.*774_*779delTTTTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00907 in 73,060 control chromosomes in the GnomAD database, including 5 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0091 (5 hom., cov: 22)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MEFV NM_000243.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.338

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.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00907 (663/73060) while in subpopulation AFR AF= 0.0298 (628/21050). AF 95% confidence interval is 0.0279. There are 5 homozygotes in gnomad4. There are 338 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 5 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEFV	NM_000243.3	c.*774_*779delTTTTTT		3_prime_UTR_variant	Exon 10 of 10	ENST00000219596.6	NP_000234.1
MEFV	NM_001198536.2	c.*1324_*1329delTTTTTT		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.*774_*779delTTTTTT		3_prime_UTR_variant	Exon 10 of 10	1	NM_000243.3	ENSP00000219596.1

Frequencies

GnomAD3 genomes AF: 0.00906 AC: 662 AN: 73050 Hom.: 5 Cov.: 22

Gnomad AFR AF: 0.0298

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000288

Gnomad OTH AF: 0.0109

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 236 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 166

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.00907 AC: 663 AN: 73060 Hom.: 5 Cov.: 22 AF XY: 0.00988 AC XY: 338 AN XY: 34216

Gnomad4 AFR AF: 0.0298

Gnomad4 AMR AF: 0.00393

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000288

Gnomad4 OTH AF: 0.0108

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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;