14-100836035-C-A

Position:

• chr14-100836035-C-A

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP6

The NR_046464.1(MEG3):​n.1080-7C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00124 in 352,058 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0012 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0013 (0 hom.)
• Consequence: MEG3 NR_046464.1 splice_region, intron
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.0560

Genes affected

MEG3 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 14-100836035-C-A is Benign according to our data. Variant chr14-100836035-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 3043544.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MEG3	NR_002766.2	n.1050-132C>A		intron_variant
MEG3	NR_003530.2	n.1300-132C>A		intron_variant
MEG3	NR_003531.3	n.1167-132C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MEG3	ENST00000398461.5	n.2912-132C>A		intron_variant		1
MEG3	ENST00000429159.6	n.1066-132C>A		intron_variant		1
MEG3	ENST00000451743.6	n.1032-132C>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.00120 AC: 183 AN: 152222 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000289

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000753

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00228

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00126 AC: 252 AN: 199718 Hom.: 0 Cov.: 0 AF XY: 0.00119 AC XY: 133 AN XY: 111298

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000101

Gnomad4 ASJ exome AF: 0.000231

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00130

Gnomad4 NFE exome AF: 0.00201

Gnomad4 OTH exome AF: 0.00115

GnomAD4 genome AF: 0.00120 AC: 183 AN: 152340 Hom.: 1 Cov.: 33 AF XY: 0.00113 AC XY: 84 AN XY: 74490

Gnomad4 AFR AF: 0.000289

Gnomad4 AMR AF: 0.000261

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000753

Gnomad4 NFE AF: 0.00228

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00122 Hom.: 0

Bravo AF: 0.00122

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

MEG3-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 28, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.9
DANN	Benign	0.72

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs141262576; hg19: chr14-101302372;