rs281865551

Variant names:

• chr16-3242380-G-A
• rs281865551
• NM_000243.3:c.*761C>T

Your query was ambiguous. Multiple possible variants found:

• chr16-3242380-G-A
• chr16-3242380-G-C
• chr16-3242380-G-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.*761C>T 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000093 (0 hom., cov: 24)
  • 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: -1.64
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEFV	NM_000243.3	c.*761C>T		3_prime_UTR_variant	Exon 10 of 10	ENST00000219596.6	NP_000234.1
MEFV	NM_001198536.2	c.*1311C>T		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	ENST00000219596.6	c.*761C>T		3_prime_UTR_variant	Exon 10 of 10	1	NM_000243.3	ENSP00000219596.1

Frequencies

GnomAD3 genomes AF: 0.0000652 AC: 7 AN: 107330 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.0000376

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000716

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000372

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 862 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 584

African (AFR) AF: 0.00 AC: 0 AN: 4

American (AMR) AF: 0.00 AC: 0 AN: 10

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6

East Asian (EAS) AF: 0.00 AC: 0 AN: 16

South Asian (SAS) AF: 0.00 AC: 0 AN: 340

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 420

Other (OTH) AF: 0.00 AC: 0 AN: 14

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000931 AC: 10 AN: 107358 Hom.: 0 Cov.: 24 AF XY: 0.000154 AC XY: 8 AN XY: 51916

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

African (AFR) AF: 0.000113 AC: 3 AN: 26604

American (AMR) AF: 0.00 AC: 0 AN: 9916

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2710

East Asian (EAS) AF: 0.00 AC: 0 AN: 3268

South Asian (SAS) AF: 0.00 AC: 0 AN: 3240

European-Finnish (FIN) AF: 0.000716 AC: 4 AN: 5588

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 112

European-Non Finnish (NFE) AF: 0.0000372 AC: 2 AN: 53832

Other (OTH) AF: 0.000729 AC: 1 AN: 1372

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.78
DANN	Benign	0.80
PhyloP100		-1.6

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: rs281865551; hg19: chr16-3292380;