rs3867498

Variant names:

• chr15-24833640-G-A
• rs3867498
• ENST00000400100.5:c.-579+3735G>A

Your query was ambiguous. Multiple possible variants found:

• chr15-24833640-G-A
• chr15-24833640-G-C
• chr15-24833640-G-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 publications found

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]

ENSG00000286110 (HGNC:):

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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SNRPN	NM_001378251.1	c.-812+3735G>A		intron_variant	Intron 2 of 13		NP_001365180.1
SNRPN	NM_001349455.2	c.-747+9817G>A		intron_variant	Intron 1 of 12		NP_001336384.1
SNRPN	NM_001349456.2	c.-654+9817G>A		intron_variant	Intron 1 of 12		NP_001336385.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNRPN	ENST00000400100.5	c.-579+3735G>A		intron_variant	Intron 2 of 12	1		ENSP00000382972.1
SNRPN	ENST00000642807.1	c.-767+3735G>A		intron_variant	Intron 2 of 13			ENSP00000495345.1
SNRPN	ENST00000645002.1	c.-878+3735G>A		intron_variant	Intron 2 of 14			ENSP00000494831.1

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

African (AFR) AF: 0.0817 AC: 3386 AN: 41428

American (AMR) AF: 0.111 AC: 1691 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.108 AC: 376 AN: 3472

East Asian (EAS) AF: 0.0149 AC: 77 AN: 5164

South Asian (SAS) AF: 0.113 AC: 545 AN: 4822

European-Finnish (FIN) AF: 0.199 AC: 2109 AN: 10572

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.181 AC: 12329 AN: 67996

Other (OTH) AF: 0.141 AC: 298 AN: 2112

Alfa AF: 0.161 Hom.: 9926

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
PhyloP100		0.35
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3867498; hg19: chr15-25078787;