rs188270533

Variant names:

• chr15-24986947-T-A
• rs188270533
• ENST00000557108.6:n.6371T>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The ENST00000551312.6(ENSG00000214265):​n.*953+4510T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00302 in 519,188 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0030 (8 hom., cov: 33)
  • Exomes 𝑓: 0.0030 (2 hom.)
• Consequence: ENSG00000214265 ENST00000551312.6 intron
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.594
• Publications: 0 publications found

Genes affected

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]

ENSG00000214265 (HGNC:):

SNORD108 (HGNC:32772): (small nucleolar RNA, C/D box 108)

PWAR5 (HGNC:30090): (Prader Willi/Angelman region RNA 5)

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BS2: High Homozygotes in GnomAd4 at 8 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000551312.6. 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
	SNORD108	NR_001292.2		n.23T>A		non_coding_transcript_exon	Exon 1 of 1
	PWAR5	NR_022008.1		n.2088T>A		non_coding_transcript_exon	Exon 1 of 1
	SNHG14	NR_146177.1		n.3624+4510T>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNHG14	ENST00000557108.6	TSL:1	n.6371T>A		non_coding_transcript_exon	Exon 3 of 3
	ENSG00000214265	ENST00000551312.6	TSL:5	n.*953+4510T>A		intron	N/A	ENSP00000451421.1
	SNORD108	ENST00000459332.1	TSL:6	n.23T>A		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes AF: 0.00303 AC: 461 AN: 152174 Hom.: 8 Cov.: 33

Gnomad AFR AF: 0.000531

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.000785

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00169

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00450

Gnomad OTH AF: 0.00383

GnomAD2 exomes AF: 0.00258 AC: 598 AN: 231822 AF XY: 0.00274

Gnomad AFR exome AF: 0.000502

Gnomad AMR exome AF: 0.00137

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00163

Gnomad NFE exome AF: 0.00459

Gnomad OTH exome AF: 0.00238

GnomAD4 exome AF: 0.00303 AC: 1110 AN: 366896 Hom.: 2 Cov.: 0 AF XY: 0.00290 AC XY: 611 AN XY: 210378

African (AFR) AF: 0.000476 AC: 5 AN: 10510

American (AMR) AF: 0.00138 AC: 50 AN: 36302

Ashkenazi Jewish (ASJ) AF: 0.0000851 AC: 1 AN: 11744

East Asian (EAS) AF: 0.00 AC: 0 AN: 13172

South Asian (SAS) AF: 0.000524 AC: 35 AN: 66766

European-Finnish (FIN) AF: 0.00218 AC: 37 AN: 16934

Middle Eastern (MID) AF: 0.000701 AC: 2 AN: 2852

European-Non Finnish (NFE) AF: 0.00488 AC: 937 AN: 191984

Other (OTH) AF: 0.00259 AC: 43 AN: 16632

GnomAD4 genome AF: 0.00302 AC: 460 AN: 152292 Hom.: 8 Cov.: 33 AF XY: 0.00271 AC XY: 202 AN XY: 74470

African (AFR) AF: 0.000529 AC: 22 AN: 41564

American (AMR) AF: 0.000784 AC: 12 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4820

European-Finnish (FIN) AF: 0.00169 AC: 18 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00450 AC: 306 AN: 68026

Other (OTH) AF: 0.00379 AC: 8 AN: 2112

Alfa AF: 0.00380 Hom.: 1

Bravo AF: 0.00299

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.4
DANN	Benign	0.79
PhyloP100		0.59
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3

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: rs188270533; hg19: chr15-25232094;