Variant chr15-24986947-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000551312.6(ENSG00000214265):n.*953+4510T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00302 in 519,188 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0030 ( 8 hom., cov: 33)

Exomes 𝑓: 0.0030 ( 2 hom. )

Consequence

ENSG00000214265
ENST00000551312.6 intron

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.594

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:

ENSG00000214265 (HGNC:):

ENSG00000214265 links:

SNORD108 (HGNC:32772): (small nucleolar RNA, C/D box 108)

SNORD108 links:

PWAR5 (HGNC:30090): (Prader Willi/Angelman region RNA 5)

PWAR5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BS2

High Homozygotes in GnomAd4 at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons
SNORD108	NR_001292.2 link	n.23T>A	non_coding_transcript_exon_variant	1/1
PWAR5	NR_022008.1 link	n.2088T>A	non_coding_transcript_exon_variant	1/1
SNHG14	NR_146177.1 link	n.3624+4510T>A	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000214265	ENST00000551312.6 link	n.*953+4510T>A		intron_variant		5		ENSP00000451421.1

Frequencies

GnomAD3 genomes

AF:

0.00303

AC:

461

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000531

Gnomad AMI

AF:

0.101

Gnomad AMR

AF:

0.000785

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00169

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00450

Gnomad OTH

AF:

0.00383

GnomAD3 exomes

AF:

0.00258

AC:

598

AN:

231822

Hom.:

AF XY:

0.00274

AC XY:

351

AN XY:

127908

show subpopulations

Gnomad AFR exome

AF:

0.000502

Gnomad AMR exome

AF:

0.00137

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000462

Gnomad FIN exome

AF:

0.00163

Gnomad NFE exome

AF:

0.00459

Gnomad OTH exome

AF:

0.00238

GnomAD4 exome

AF:

0.00303

AC:

1110

AN:

366896

Hom.:

Cov.:

AF XY:

0.00290

AC XY:

611

AN XY:

210378

show subpopulations

Gnomad4 AFR exome

AF:

0.000476

Gnomad4 AMR exome

AF:

0.00138

Gnomad4 ASJ exome

AF:

0.0000851

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000524

Gnomad4 FIN exome

AF:

0.00218

Gnomad4 NFE exome

AF:

0.00488

Gnomad4 OTH exome

AF:

0.00259

GnomAD4 genome

AF:

0.00302

AC:

460

AN:

152292

Hom.:

Cov.:

AF XY:

0.00271

AC XY:

202

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.000529

Gnomad4 AMR

AF:

0.000784

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00169

Gnomad4 NFE

AF:

0.00450

Gnomad4 OTH

AF:

0.00379

Alfa

AF:

0.00380

Hom.:

Bravo

AF:

0.00299

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

5.4

DANN

Benign

0.79

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over