rs2075814

Positions:

• chr15-24920629-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The ENST00000400097.5(SNRPN):​c.-391+505A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 152,196 control chromosomes in the GnomAD database, including 992 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.10 (992 hom., cov: 32)
  • Exomes 𝑓: 0.042 (0 hom.)
• Consequence: SNRPN ENST00000400097.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.343

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 15-24920629-A-G is Benign according to our data. Variant chr15-24920629-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNHG14	NR_146177.1	n.512+505A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNRPN	ENST00000400097.5	c.-391+505A>G		intron_variant		1		P1
SNRPN	ENST00000400100.5	c.-391+505A>G		intron_variant		1		P1
SNRPN	ENST00000642807.1	c.-579+505A>G		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15600 AN: 152052 Hom.: 996 Cov.: 32

Gnomad AFR AF: 0.0514

Gnomad AMI AF: 0.195

Gnomad AMR AF: 0.0996

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.322

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.0960

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.113

GnomAD4 exome AF: 0.0417 AC: 1 AN: 24 Hom.: 0 AF XY: 0.0556 AC XY: 1 AN XY: 18

Gnomad4 SAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.0500

GnomAD4 genome AF: 0.102 AC: 15586 AN: 152172 Hom.: 992 Cov.: 32 AF XY: 0.103 AC XY: 7660 AN XY: 74390

Gnomad4 AFR AF: 0.0513

Gnomad4 AMR AF: 0.0995

Gnomad4 ASJ AF: 0.164

Gnomad4 EAS AF: 0.322

Gnomad4 SAS AF: 0.100

Gnomad4 FIN AF: 0.0960

Gnomad4 NFE AF: 0.114

Gnomad4 OTH AF: 0.112

Alfa AF: 0.115 Hom.: 1495

Bravo AF: 0.105

Asia WGS AF: 0.183 AC: 635 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.7
DANN	Benign	0.29

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: rs2075814; hg19: chr15-25165776;