16-3257201-G-C

Variant names:

• chr16-3257201-G-C
• rs11466012
• ENST00000956137.1:c.-614C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000956137.1(MEFV):​c.-614C>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0184 in 152,326 control chromosomes in the GnomAD database, including 82 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.018 (82 hom., cov: 32)
• Consequence: MEFV ENST00000956137.1 upstream_gene
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.500
• Publications: 2 publications found

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]

MEFV Gene-Disease associations (from GenCC):

• familial Mediterranean fever

  Inheritance: AD, AR, SD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, Myriad Women’s Health, ClinGen
• autosomal recessive familial Mediterranean fever

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
• familial Mediterranean fever, autosomal dominant

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 16-3257201-G-C is Benign according to our data. Variant chr16-3257201-G-C is described in ClinVar as Benign. ClinVar VariationId is 458003.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.06 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000956137.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEFV	ENST00000956137.1		c.-614C>G		upstream_gene	N/A	ENSP00000626196.1

Frequencies

GnomAD3 genomes AF: 0.0184 AC: 2803 AN: 152208 Hom.: 82 Cov.: 32

Gnomad AFR AF: 0.0622

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00831

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000897

Gnomad OTH AF: 0.0153

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

GnomAD4 genome AF: 0.0184 AC: 2804 AN: 152326 Hom.: 82 Cov.: 32 AF XY: 0.0170 AC XY: 1266 AN XY: 74482

African (AFR) AF: 0.0620 AC: 2577 AN: 41570

American (AMR) AF: 0.00830 AC: 127 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.000897 AC: 61 AN: 68020

Other (OTH) AF: 0.0151 AC: 32 AN: 2116

Alfa AF: 0.000286 Hom.: 0

Bravo AF: 0.0212

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Familial Mediterranean fever (3)
-	-	1	Acute febrile neutrophilic dermatosis (1)
-	-	1	Familial Mediterranean fever, autosomal dominant (1)
-	-	1	Familial Mediterranean fever;C0085077:Acute febrile neutrophilic dermatosis;C1851347:Familial Mediterranean fever, autosomal dominant (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.68
DANN	Benign	0.45
PhyloP100		-0.50

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11466012; hg19: chr16-3307201;