rs941576

Positions:

• chr14-100839708-A-G
• chr14-100839708-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000398461.5(MEG3):​n.3045+3408A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 151,982 control chromosomes in the GnomAD database, including 15,283 homozygotes. 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 0.44 (15283 hom., cov: 32)
• Consequence: MEG3 ENST00000398461.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.755

Genes affected

MEG3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MEG3	NR_002766.2	n.1183+3408A>G		intron_variant
MEG3	NR_003530.2	n.1433+3408A>G		intron_variant
MEG3	NR_003531.3	n.1300+3408A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MEG3	ENST00000398461.5	n.3045+3408A>G		intron_variant		1
MEG3	ENST00000429159.6	n.1199+3408A>G		intron_variant		1
MEG3	ENST00000451743.6	n.1165+3408A>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.445 AC: 67564 AN: 151864 Hom.: 15278 Cov.: 32

Gnomad AFR AF: 0.449

Gnomad AMI AF: 0.414

Gnomad AMR AF: 0.466

Gnomad ASJ AF: 0.417

Gnomad EAS AF: 0.313

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.522

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.448

Gnomad OTH AF: 0.443

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.445 AC: 67613 AN: 151982 Hom.: 15283 Cov.: 32 AF XY: 0.443 AC XY: 32927 AN XY: 74258

Gnomad4 AFR AF: 0.449

Gnomad4 AMR AF: 0.467

Gnomad4 ASJ AF: 0.417

Gnomad4 EAS AF: 0.314

Gnomad4 SAS AF: 0.299

Gnomad4 FIN AF: 0.522

Gnomad4 NFE AF: 0.448

Gnomad4 OTH AF: 0.442

Alfa AF: 0.439 Hom.: 3123

Bravo AF: 0.446

Asia WGS AF: 0.303 AC: 1051 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.4
DANN	Benign	0.57

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs941576; hg19: chr14-101306045;