15-24954621-T-C

Position:

• chr15-24954621-T-C

Variant summary

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

The NM_001378251.1(SNRPN):​c.-548-7493T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 152,136 control chromosomes in the GnomAD database, including 8,906 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 0.34 (8906 hom., cov: 33)
• Consequence: SNRPN NM_001378251.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0330

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.494 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNRPN	NM_001378251.1	c.-548-7493T>C		intron_variant			NP_001365180.1
SNRPN	NM_001349454.2	c.-370-4117T>C		intron_variant			NP_001336383.1
SNRPN	NM_001349455.2	c.-390-7493T>C		intron_variant			NP_001336384.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNRPN	ENST00000400097.5	c.-390-7493T>C		intron_variant		1		ENSP00000382969.1
SNRPN	ENST00000400100.5	c.-390-7493T>C		intron_variant		1		ENSP00000382972.1
SNRPN	ENST00000642807.1	c.-390-7493T>C		intron_variant				ENSP00000495345.1

Frequencies

GnomAD3 genomes AF: 0.335 AC: 50981 AN: 152018 Hom.: 8894 Cov.: 33

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.307

Gnomad AMR AF: 0.418

Gnomad ASJ AF: 0.400

Gnomad EAS AF: 0.511

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.354

Gnomad OTH AF: 0.344

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

GnomAD4 genome AF: 0.335 AC: 51005 AN: 152136 Hom.: 8906 Cov.: 33 AF XY: 0.332 AC XY: 24686 AN XY: 74382

Gnomad4 AFR AF: 0.274

Gnomad4 AMR AF: 0.420

Gnomad4 ASJ AF: 0.400

Gnomad4 EAS AF: 0.511

Gnomad4 SAS AF: 0.165

Gnomad4 FIN AF: 0.304

Gnomad4 NFE AF: 0.354

Gnomad4 OTH AF: 0.341

Alfa AF: 0.350 Hom.: 12834

Bravo AF: 0.349

Asia WGS AF: 0.320 AC: 1110 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	4.5
DANN	Benign	0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs220030; hg19: chr15-25199768;