rs1316887692

Variant names:

• chr16-3242139-C-G
• rs1316887692
• NM_000243.3:c.*1002G>C

Your query was ambiguous. Multiple possible variants found:

• chr16-3242139-C-G
• chr16-3242139-C-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000243.3(MEFV):​c.*1002G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00068 (0 hom., cov: 30)
  • Exomes 𝑓: 0.00094 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MEFV NM_000243.3 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.532
• 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):

• autosomal recessive familial Mediterranean fever

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

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

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

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).

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.*1002G>C		3_prime_UTR	Exon 10 of 10	NP_000234.1	O15553-2
	MEFV	NM_001198536.2		c.*1552G>C		3_prime_UTR	Exon 9 of 9	NP_001185465.2	O15553-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEFV	ENST00000219596.6	TSL:1 MANE Select	c.*1002G>C		3_prime_UTR	Exon 10 of 10	ENSP00000219596.1	O15553-2
	MEFV	ENST00000956137.1		c.*1002G>C		3_prime_UTR	Exon 10 of 10	ENSP00000626196.1
	MEFV	ENST00000339854.8	TSL:5	c.*1002G>C		3_prime_UTR	Exon 10 of 10	ENSP00000339639.4	F8W6Z2

Frequencies

GnomAD3 genomes AF: 0.000683 AC: 96 AN: 140542 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.000826

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000705

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00329

Gnomad SAS AF: 0.000690

Gnomad FIN AF: 0.00130

Gnomad MID AF: 0.00935

Gnomad NFE AF: 0.000326

Gnomad OTH AF: 0.00106

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000940 AC: 32 AN: 34032 Hom.: 0 Cov.: 0 AF XY: 0.000977 AC XY: 21 AN XY: 21500

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 304

American (AMR) AF: 0.00165 AC: 2 AN: 1212

Ashkenazi Jewish (ASJ) AF: 0.00114 AC: 1 AN: 876

East Asian (EAS) AF: 0.00 AC: 0 AN: 168

South Asian (SAS) AF: 0.000785 AC: 9 AN: 11460

European-Finnish (FIN) AF: 0.000442 AC: 1 AN: 2260

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 104

European-Non Finnish (NFE) AF: 0.00110 AC: 18 AN: 16394

Other (OTH) AF: 0.000797 AC: 1 AN: 1254

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000675 AC: 95 AN: 140646 Hom.: 0 Cov.: 30 AF XY: 0.000654 AC XY: 45 AN XY: 68812

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000850 AC: 32 AN: 37646

American (AMR) AF: 0.000704 AC: 10 AN: 14204

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3336

East Asian (EAS) AF: 0.00330 AC: 15 AN: 4548

South Asian (SAS) AF: 0.000461 AC: 2 AN: 4336

European-Finnish (FIN) AF: 0.00130 AC: 12 AN: 9260

Middle Eastern (MID) AF: 0.00980 AC: 2 AN: 204

European-Non Finnish (NFE) AF: 0.000326 AC: 21 AN: 64346

Other (OTH) AF: 0.000525 AC: 1 AN: 1904

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00306 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Familial Mediterranean fever (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.70
DANN	Benign	0.44
PhyloP100		-0.53

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: rs1316887692; hg19: chr16-3292139;