rs1231124

Variant names:

• chr16-3244678-G-A
• rs1231124
• NM_000243.3:c.1611-90C>T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000243.3(MEFV):​c.1611-90C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.421 in 945,006 control chromosomes in the GnomAD database, including 86,632 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.41 (12998 hom., cov: 32)
  • Exomes 𝑓: 0.42 (73634 hom.)
• Consequence: MEFV NM_000243.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.06

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 16-3244678-G-A is Benign according to our data. Variant chr16-3244678-G-A is described in ClinVar as [Benign]. Clinvar id is 676934.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEFV	NM_000243.3	c.1611-90C>T		intron_variant	Intron 6 of 9	ENST00000219596.6	NP_000234.1
MEFV	NM_001198536.2	c.978-90C>T		intron_variant	Intron 5 of 8		NP_001185465.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEFV	ENST00000219596.6	c.1611-90C>T		intron_variant	Intron 6 of 9	1	NM_000243.3	ENSP00000219596.1

Frequencies

GnomAD3 genomes AF: 0.409 AC: 62069 AN: 151852 Hom.: 12999 Cov.: 32

Gnomad AFR AF: 0.338

Gnomad AMI AF: 0.599

Gnomad AMR AF: 0.375

Gnomad ASJ AF: 0.436

Gnomad EAS AF: 0.386

Gnomad SAS AF: 0.271

Gnomad FIN AF: 0.441

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.461

Gnomad OTH AF: 0.424

GnomAD4 exome AF: 0.423 AC: 335835 AN: 793036 Hom.: 73634 AF XY: 0.420 AC XY: 176019 AN XY: 419218

Gnomad4 AFR exome AF: 0.341

Gnomad4 AMR exome AF: 0.274

Gnomad4 ASJ exome AF: 0.442

Gnomad4 EAS exome AF: 0.386

Gnomad4 SAS exome AF: 0.287

Gnomad4 FIN exome AF: 0.440

Gnomad4 NFE exome AF: 0.458

Gnomad4 OTH exome AF: 0.428

GnomAD4 genome AF: 0.409 AC: 62087 AN: 151970 Hom.: 12998 Cov.: 32 AF XY: 0.404 AC XY: 30039 AN XY: 74276

Gnomad4 AFR AF: 0.338

Gnomad4 AMR AF: 0.375

Gnomad4 ASJ AF: 0.436

Gnomad4 EAS AF: 0.386

Gnomad4 SAS AF: 0.273

Gnomad4 FIN AF: 0.441

Gnomad4 NFE AF: 0.461

Gnomad4 OTH AF: 0.423

Alfa AF: 0.431 Hom.: 1778

Bravo AF: 0.400

Asia WGS AF: 0.307 AC: 1068 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 19, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not specified Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 44% of patients studied by a panel of primary immunodeficiencies. Number of patients: 42. Only high quality variants are reported. -

Familial Mediterranean fever, autosomal dominant Benign:1

Jul 01, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Familial Mediterranean fever Benign:1

Jul 01, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.50
DANN	Benign	0.55

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: rs1231124; hg19: chr16-3294678; COSMIC: COSV54822651; COSMIC: COSV54822651;