rs75330474

Positions:

• chr14-101056252-C-T

Variant summary

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

The ENST00000699461.1(MEG9):​n.381+8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0157 in 533,574 control chromosomes in the GnomAD database, including 203 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 0.025 (108 hom., cov: 33)
  • Exomes 𝑓: 0.012 (95 hom.)
• Consequence: MEG9 ENST00000699461.1 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.47

Genes affected

MIR323B (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0683 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MIR323B	NR_036133.1	n.34C>T		non_coding_transcript_exon_variant	1/1
MIR323B	unassigned_transcript_2435	n.20C>T		non_coding_transcript_exon_variant	1/1
MIR323B	unassigned_transcript_2436	n.-17C>T		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIR323B	ENST00000385269.2	n.34C>T		non_coding_transcript_exon_variant	1/1	6
MEG9	ENST00000699461.1	n.381+8C>T		splice_region_variant, intron_variant
MEG9	ENST00000699460.1	n.*8C>T		downstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.0249 AC: 3788 AN: 152142 Hom.: 108 Cov.: 33

Gnomad AFR AF: 0.0705

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00622

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.0528

Gnomad SAS AF: 0.0292

Gnomad FIN AF: 0.00687

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00347

Gnomad OTH AF: 0.0196

GnomAD3 exomes AF: 0.0150 AC: 3765 AN: 250602 Hom.: 79 AF XY: 0.0145 AC XY: 1961 AN XY: 135668

Gnomad AFR exome AF: 0.0704

Gnomad AMR exome AF: 0.00402

Gnomad ASJ exome AF: 0.00269

Gnomad EAS exome AF: 0.0519

Gnomad SAS exome AF: 0.0277

Gnomad FIN exome AF: 0.00599

Gnomad NFE exome AF: 0.00407

Gnomad OTH exome AF: 0.0114

GnomAD4 exome AF: 0.0120 AC: 4588 AN: 381314 Hom.: 95 Cov.: 0 AF XY: 0.0130 AC XY: 2816 AN XY: 217154

Gnomad4 AFR exome AF: 0.0705

Gnomad4 AMR exome AF: 0.00386

Gnomad4 ASJ exome AF: 0.00272

Gnomad4 EAS exome AF: 0.0482

Gnomad4 SAS exome AF: 0.0276

Gnomad4 FIN exome AF: 0.00579

Gnomad4 NFE exome AF: 0.00432

Gnomad4 OTH exome AF: 0.0106

GnomAD4 genome AF: 0.0249 AC: 3792 AN: 152260 Hom.: 108 Cov.: 33 AF XY: 0.0240 AC XY: 1785 AN XY: 74436

Gnomad4 AFR AF: 0.0704

Gnomad4 AMR AF: 0.00628

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.0527

Gnomad4 SAS AF: 0.0290

Gnomad4 FIN AF: 0.00687

Gnomad4 NFE AF: 0.00347

Gnomad4 OTH AF: 0.0194

Alfa AF: 0.0120 Hom.: 24

Bravo AF: 0.0269

Asia WGS AF: 0.0540 AC: 188 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	8.2
DANN	Benign	0.93

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs75330474; hg19: chr14-101522589;