Genetic Variant SNHG14:n.381C>T (chr15-25201209-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000424333.6(SNHG14):n.381C>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
ENST00000424333.6 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.481

Publications

4 publications found

Variant links:

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]

SNHG14 links:

SNORD115-17 (HGNC:33036): (small nucleolar RNA, C/D box 115-17)

SNORD115-17 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SNHG14	NR_146177.1 link	n.13308C>T		non_coding_transcript_exon_variant	Exon 93 of 148
SNORD115-17	NR_003309.1 link	n.-114C>T		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
SNHG14	ENST00000424333.6 link	n.381C>T	non_coding_transcript_exon_variant	Exon 5 of 54	1
SNHG14	ENST00000424208.5 link	n.1931C>T	non_coding_transcript_exon_variant	Exon 21 of 34	5
SNHG14	ENST00000653489.1 link	n.295C>T	non_coding_transcript_exon_variant	Exon 4 of 59

Frequencies

GnomAD3 genomes

AF:

0.0248

AC:

3780

AN:

152180

Hom.:

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.00754

AC XY:

1507

AN XY:

199972

show subpopulations

African (AFR)

AF:

0.0674

AC:

610

AN:

9052

American (AMR)

AF:

0.00960

AC:

288

AN:

30004

Ashkenazi Jewish (ASJ)

AF:

0.0219

AC:

233

AN:

10616

East Asian (EAS)

AF:

0.00

AC:

AN:

13020

South Asian (SAS)

AF:

0.00186

AC:

118

AN:

63392

European-Finnish (FIN)

AF:

0.00726

AC:

121

AN:

16678

Middle Eastern (MID)

AF:

0.0198

AC:

AN:

2626

European-Non Finnish (NFE)

AF:

0.00690

AC:

1283

AN:

185886

Other (OTH)

AF:

0.0137

AC:

216

AN:

15744

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

130

260

391

521

651

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0250

AC:

3811

AN:

152298

Hom.:

Cov.:

AF XY:

0.0249

AC XY:

1851

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.0689

AC:

2862

AN:

41550

American (AMR)

AF:

0.0170

AC:

260

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0259

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5162

South Asian (SAS)

AF:

0.00249

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00744

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00673

AC:

458

AN:

68040

Other (OTH)

AF:

0.0203

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

179

359

538

718

897

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

160

200

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0220

Hom.:

Bravo

AF:

0.0266

Asia WGS

AF:

0.00751

AC:

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

(source)

DANN

Benign

0.27

PhyloP100

-0.48

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over