16-3254411-G-C

Position:

• chr16-3254411-G-C

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_000243.3(MEFV):​c.657C>G​(p.Gly219Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. G219G) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000036 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MEFV NM_000243.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.628

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 -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 16-3254411-G-C is Benign according to our data. Variant chr16-3254411-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2883169.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.628 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MEFV	NM_000243.3	c.657C>G	p.Gly219Gly	synonymous_variant	2/10	ENST00000219596.6	NP_000234.1
MEFV	NM_001198536.2	c.277+1900C>G		intron_variant			NP_001185465.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MEFV	ENST00000219596.6	c.657C>G	p.Gly219Gly	synonymous_variant	2/10	1	NM_000243.3	ENSP00000219596.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.000357 AC: 84 AN: 235542 Hom.: 0 AF XY: 0.000262 AC XY: 34 AN XY: 129592

Gnomad AFR exome AF: 0.000792

Gnomad AMR exome AF: 0.000148

Gnomad ASJ exome AF: 0.000206

Gnomad EAS exome AF: 0.000625

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000793

Gnomad NFE exome AF: 0.000354

Gnomad OTH exome AF: 0.000346

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000364 AC: 53 AN: 1456344 Hom.: 0 Cov.: 32 AF XY: 0.0000414 AC XY: 30 AN XY: 724282

Gnomad4 AFR exome AF: 0.0000300

Gnomad4 AMR exome AF: 0.000114

Gnomad4 ASJ exome AF: 0.0000767

Gnomad4 EAS exome AF: 0.000255

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.000430

Gnomad4 NFE exome AF: 0.00000990

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Familial Mediterranean fever Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

May 27, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.88
DANN	Benign	0.46

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: rs104895182; hg19: chr16-3304411;