rs3867498

chr15-24833640-G-A

Variant summary

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

The ENST00000400100.5(SNRPN):c.-579+3735G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 152,074 control chromosomes in the GnomAD database, including 1,681 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 0.14 (1681 hom., cov: 33)
• Consequence: SNRPN ENST00000400100.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.349

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]

SNHG14 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNHG14	NR_146177.1	n.324+3735G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNRPN	ENST00000400100.5	c.-579+3735G>A		intron_variant		1		P1
SNRPN	ENST00000642807.1	c.-767+3735G>A		intron_variant				P1
SNRPN	ENST00000645002.1	c.-878+3735G>A		intron_variant				P1
SNRPN	ENST00000400098.6	n.187+9817G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.138 AC: 21039 AN: 151956 Hom.: 1681 Cov.: 33

Gnomad AFR AF: 0.0819

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.0147

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.143

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.138 AC: 21042 AN: 152074 Hom.: 1681 Cov.: 33 AF XY: 0.138 AC XY: 10241 AN XY: 74338

Gnomad4 AFR AF: 0.0817

Gnomad4 AMR AF: 0.111

Gnomad4 ASJ AF: 0.108

Gnomad4 EAS AF: 0.0149

Gnomad4 SAS AF: 0.113

Gnomad4 FIN AF: 0.199

Gnomad4 NFE AF: 0.181

Gnomad4 OTH AF: 0.141

Alfa AF: 0.162 Hom.: 4983

Bravo AF: 0.128

Asia WGS AF: 0.0720 AC: 252 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	4.8
Dann	Benign	0.41

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

Other links and lift over

dbSNP: rs3867498; hg19: chr15-25078787;