Variant 15-24829910-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000400100.5(SNRPN):c.-579+5G>A variant causes a splice donor 5th base, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 152,030 control chromosomes in the GnomAD database, including 1,495 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1494 hom., cov: 32)

Exomes 𝑓: 0.15 ( 1 hom. )

Consequence

SNRPN
ENST00000400100.5 splice_donor_5th_base, intron

Scores

Splicing: ADA: 0.00002453

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.39

Variant links:

Genes affected

SNRPN (HGNC:11164): (small nuclear ribonucleoprotein polypeptide N) This gene is located within the Prader-Willi Syndrome critical region on chromosome 15 and is imprinted and expressed from the paternal allele. It encodes a component of the small nuclear ribonucleoprotein complex, which functions in pre-mRNA processing and may contribute to tissue-specific alternative splicing. Alternative promoter use and alternative splicing result in a multitude of transcript variants encoding the same protein. Transcript variants that initiate at the CpG island-associated imprinting center may be bicistronic and also encode the SNRPN upstream reading frame protein (SNURF) from an upstream open reading frame. In addition, long spliced transcripts for small nucleolar RNA host gene 14 (SNHG14) may originate from the promoters at this locus and share exons with this gene. Alterations in this region are associated with parental imprint switch failure, which may cause Angelman syndrome or Prader-Willi syndrome. [provided by RefSeq, Mar 2017]

SNRPN links:

SNHG14 (HGNC:):

SNHG14 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BP6

Variant 15-24829910-G-A is Benign according to our data. Variant chr15-24829910-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 315435.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNHG14	NR_146177.1 linkuse as main transcript	n.324+5G>A		splice_donor_5th_base_variant, intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	Protein	Appris	UniProt
SNRPN	ENST00000400100.5 linkuse as main transcript	c.-579+5G>A	splice_donor_5th_base_variant, intron_variant	1	ENSP00000382972	P1	P63162-1
SNRPN	ENST00000642807.1 linkuse as main transcript	c.-767+5G>A	splice_donor_5th_base_variant, intron_variant		ENSP00000495345	P1	P63162-1
SNRPN	ENST00000645002.1 linkuse as main transcript	c.-878+5G>A	splice_donor_5th_base_variant, intron_variant		ENSP00000494831	P1	P63162-1
SNRPN	ENST00000400098.6 linkuse as main transcript	n.187+6087G>A	intron_variant, non_coding_transcript_variant	4

Frequencies

GnomAD3 genomes

AF:

0.130

AC:

19659

AN:

151800

Hom.:

1485

Cov.:

show subpopulations

Gnomad AFR

AF:

0.187

Gnomad AMI

AF:

0.186

Gnomad AMR

AF:

0.0955

Gnomad ASJ

AF:

0.186

Gnomad EAS

AF:

0.0273

Gnomad SAS

AF:

0.0525

Gnomad FIN

AF:

0.166

Gnomad MID

AF:

0.171

Gnomad NFE

AF:

0.106

Gnomad OTH

AF:

0.125

GnomAD4 exome

AF:

0.152

AC:

AN:

112

Hom.:

Cov.:

AF XY:

0.161

AC XY:

AN XY:

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.224

Gnomad4 NFE exome

AF:

0.0833

Gnomad4 OTH exome

AF:

0.125

GnomAD4 genome

AF:

0.130

AC:

19678

AN:

151918

Hom.:

1494

Cov.:

AF XY:

0.130

AC XY:

9653

AN XY:

74232

show subpopulations

Gnomad4 AFR

AF:

0.187

Gnomad4 AMR

AF:

0.0954

Gnomad4 ASJ

AF:

0.186

Gnomad4 EAS

AF:

0.0271

Gnomad4 SAS

AF:

0.0519

Gnomad4 FIN

AF:

0.166

Gnomad4 NFE

AF:

0.106

Gnomad4 OTH

AF:

0.123

Alfa

AF:

0.0705

Hom.:

101

Bravo

AF:

0.129

Asia WGS

AF:

0.0470

AC:

168

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Autism spectrum disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.013

DANN

Benign

0.31

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000025

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.70

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.70

Position offset: -5

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