rs7170796

Variant names:

• chr15-24829812-T-C
• rs7170796
• ENST00000400100.5:c.-672T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001378251.1(SNRPN):​c.-905T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 151,978 control chromosomes in the GnomAD database, including 1,751 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (1751 hom., cov: 32)
  • Exomes 𝑓: 0.15 (0 hom.)
• Consequence: SNRPN NM_001378251.1 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.69
• Publications: 7 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BP6: Variant 15-24829812-T-C is Benign according to our data. Variant chr15-24829812-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 315431.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378251.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNRPN	NM_001378251.1		c.-905T>C		5_prime_UTR	Exon 2 of 14	NP_001365180.1	P63162-2
	SNRPN	NM_001349457.2		c.-840T>C		5_prime_UTR	Exon 2 of 14	NP_001336386.1	X5DP00
	SNRPN	NM_001349458.2		c.-672T>C		5_prime_UTR	Exon 2 of 13	NP_001336387.1	P63162-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNRPN	ENST00000400100.5	TSL:1	c.-672T>C		5_prime_UTR	Exon 2 of 13	ENSP00000382972.1	P63162-1
	SNRPN	ENST00000642807.1		c.-860T>C		5_prime_UTR	Exon 2 of 14	ENSP00000495345.1	P63162-1
	SNRPN	ENST00000645002.1		c.-971T>C		5_prime_UTR	Exon 2 of 15	ENSP00000494831.1	P63162-1

Frequencies

GnomAD3 genomes AF: 0.138 AC: 20883 AN: 151812 Hom.: 1735 Cov.: 32

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.187

Gnomad AMR AF: 0.0978

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.0275

Gnomad SAS AF: 0.0533

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.128

GnomAD4 exome AF: 0.146 AC: 7 AN: 48 Hom.: 0 Cov.: 0 AF XY: 0.156 AC XY: 5 AN XY: 32

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AF: 0.167 AC: 2 AN: 12

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.133 AC: 4 AN: 30

Other (OTH) AF: 0.250 AC: 1 AN: 4

GnomAD4 genome AF: 0.138 AC: 20924 AN: 151930 Hom.: 1751 Cov.: 32 AF XY: 0.138 AC XY: 10208 AN XY: 74234

African (AFR) AF: 0.216 AC: 8931 AN: 41318

American (AMR) AF: 0.0976 AC: 1493 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.187 AC: 649 AN: 3472

East Asian (EAS) AF: 0.0273 AC: 141 AN: 5160

South Asian (SAS) AF: 0.0527 AC: 254 AN: 4820

European-Finnish (FIN) AF: 0.165 AC: 1745 AN: 10556

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.106 AC: 7223 AN: 67996

Other (OTH) AF: 0.127 AC: 268 AN: 2112

Alfa AF: 0.129 Hom.: 183

Bravo AF: 0.139

Asia WGS AF: 0.0550 AC: 195 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Autism spectrum disorder (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.2
DANN	Benign	0.40
PhyloP100		-1.7
Mutation Taster		=300/0	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: rs7170796; hg19: chr15-25074959;