rs2739771

chr15-25201209-C-T

Variant summary

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

The NR_146177.1(SNHG14):n.13308C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0135 in 499,316 control chromosomes in the GnomAD database, including 125 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 (92 hom., cov: 33)
  • Exomes 𝑓: 0.0084 (33 hom.)
• Consequence: SNHG14 NR_146177.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.481

Genes affected

SNHG14 (HGNC:37462): (small nucleolar RNA host gene 14) This gene is located within the Prader-Willi critical region and produces a long, spliced paternally-imprinted RNA that initiates within a common upstream promoter region shared by the SNRPN (small nuclear ribonucleoprotein polypeptide N) and SNURF genes. This transcript serves as a host RNA for the small nucleolar RNA, C/D box 115 and 116 clusters. This RNA extends in antisense into the region of the ubiquitin protein ligase E3A gene (UBE3A), and is thought to regulate imprinted expression of UBE3A in the brain. This transcript undergoes extensive alternative splicing, and may initiate and terminate at multiple locations within this genomic region. The full-length structure of all splice forms is not determined. [provided by RefSeq, Mar 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0668 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNHG14	NR_146177.1	n.13308C>T		non_coding_transcript_exon_variant	93/148

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNHG14	ENST00000424333.6	n.381C>T		non_coding_transcript_exon_variant	5/54	1
SNHG14	ENST00000656420.1	n.850C>T		non_coding_transcript_exon_variant	7/57
SNHG14	ENST00000424208.5	n.1931C>T		non_coding_transcript_exon_variant	21/34	5
SNHG14	ENST00000653489.1	n.295C>T		non_coding_transcript_exon_variant	4/59

Frequencies

GnomAD3 genomes AF: 0.0248 AC: 3780 AN: 152180 Hom.: 88 Cov.: 33

Gnomad AFR AF: 0.0684

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0170

Gnomad ASJ AF: 0.0259

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00228

Gnomad FIN AF: 0.00744

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00672

Gnomad OTH AF: 0.0201

GnomAD4 exome AF: 0.00842 AC: 2921 AN: 347018 Hom.: 33 Cov.: 0 AF XY: 0.00754 AC XY: 1507 AN XY: 199972

Gnomad4 AFR exome AF: 0.0674

Gnomad4 AMR exome AF: 0.00960

Gnomad4 ASJ exome AF: 0.0219

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00186

Gnomad4 FIN exome AF: 0.00726

Gnomad4 NFE exome AF: 0.00690

Gnomad4 OTH exome AF: 0.0137

GnomAD4 genome AF: 0.0250 AC: 3811 AN: 152298 Hom.: 92 Cov.: 33 AF XY: 0.0249 AC XY: 1851 AN XY: 74462

Gnomad4 AFR AF: 0.0689

Gnomad4 AMR AF: 0.0170

Gnomad4 ASJ AF: 0.0259

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00249

Gnomad4 FIN AF: 0.00744

Gnomad4 NFE AF: 0.00673

Gnomad4 OTH AF: 0.0203

Alfa AF: 0.0206 Hom.: 15

Bravo AF: 0.0266

Asia WGS AF: 0.00751 AC: 26 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	2.6
Dann	Benign	0.27

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2739771; hg19: chr15-25446356;