rs11466030

Variant names:

• chr16-3246998-G-A
• rs11466030
• NM_000243.3:c.1587+18C>T

Your query was ambiguous. Multiple possible variants found:

• chr16-3246998-G-A
• chr16-3246998-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_000243.3(MEFV):​c.1587+18C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00151 in 1,612,596 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0082 (20 hom., cov: 32)
  • Exomes 𝑓: 0.00081 (13 hom.)
• Consequence: MEFV NM_000243.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: -1.68
• Publications: 0 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=-0.93).
• BP6: Variant 16-3246998-G-A is Benign according to our data. Variant chr16-3246998-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 445588.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00825 (1256/152292) while in subpopulation AFR AF = 0.0271 (1128/41560). AF 95% confidence interval is 0.0258. There are 20 homozygotes in GnomAd4. There are 602 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 20 AR,AD,SD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000243.3. 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
	MEFV	NM_000243.3	MANE Select	c.1587+18C>T		intron	N/A	NP_000234.1
	MEFV	NM_001198536.2		c.954+18C>T		intron	N/A	NP_001185465.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEFV	ENST00000219596.6	TSL:1 MANE Select	c.1587+18C>T		intron	N/A	ENSP00000219596.1
	MEFV	ENST00000541159.5	TSL:1	c.954+18C>T		intron	N/A	ENSP00000438711.1
	MEFV	ENST00000539145.5	TSL:1	n.*220+18C>T		intron	N/A	ENSP00000444471.1

Frequencies

GnomAD3 genomes AF: 0.00823 AC: 1253 AN: 152174 Hom.: 20 Cov.: 32

Gnomad AFR AF: 0.0271

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00668

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00718

GnomAD2 exomes AF: 0.00248 AC: 621 AN: 250266 AF XY: 0.00176

Gnomad AFR exome AF: 0.0300

Gnomad AMR exome AF: 0.00307

Gnomad ASJ exome AF: 0.0000993

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000160

Gnomad OTH exome AF: 0.000980

GnomAD4 exome AF: 0.000807 AC: 1178 AN: 1460304 Hom.: 13 Cov.: 30 AF XY: 0.000709 AC XY: 515 AN XY: 726520

African (AFR) AF: 0.0248 AC: 830 AN: 33438

American (AMR) AF: 0.00322 AC: 144 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26130

East Asian (EAS) AF: 0.000151 AC: 6 AN: 39692

South Asian (SAS) AF: 0.0000580 AC: 5 AN: 86222

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53380

Middle Eastern (MID) AF: 0.000521 AC: 3 AN: 5762

European-Non Finnish (NFE) AF: 0.0000567 AC: 63 AN: 1110612

Other (OTH) AF: 0.00207 AC: 125 AN: 60348

GnomAD4 genome AF: 0.00825 AC: 1256 AN: 152292 Hom.: 20 Cov.: 32 AF XY: 0.00808 AC XY: 602 AN XY: 74460

African (AFR) AF: 0.0271 AC: 1128 AN: 41560

American (AMR) AF: 0.00667 AC: 102 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68016

Other (OTH) AF: 0.00710 AC: 15 AN: 2112

Alfa AF: 0.00698 Hom.: 3

Bravo AF: 0.00894

Asia WGS AF: 0.0120 AC: 40 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not provided (5)
-	-	3	Familial Mediterranean fever (3)
-	-	1	Acute febrile neutrophilic dermatosis (1)
-	-	1	Familial Mediterranean fever, autosomal dominant (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.072
DANN	Benign	0.36
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs11466030; hg19: chr16-3296998; COSMIC: COSV106055104;