rs16416

chr15-25120022-CACAG-Cchr15-25120022-CACAG-CACAGACAG

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NR_023915.1(IPW):n.2048_2051del variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.517 in 151,590 control chromosomes in the GnomAD database, including 21,750 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.52 (21750 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: IPW NR_023915.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.14

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]

IPW (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.627 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IPW	NR_023915.1	n.2048_2051del		non_coding_transcript_exon_variant	3/3
SNHG14	NR_146177.1	n.10396+1644_10396+1647del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNHG14	ENST00000626200.3	n.1347_1350del		non_coding_transcript_exon_variant	5/5	1
SNHG14	ENST00000549804.7	n.5394_5397del		non_coding_transcript_exon_variant	33/33	5
SNHG14	ENST00000640631.2	n.12668_12671del		non_coding_transcript_exon_variant	38/38	5

Frequencies

GnomAD3 genomes AF: 0.517 AC: 78309 AN: 151472 Hom.: 21757 Cov.: 0

Gnomad AFR AF: 0.328

Gnomad AMI AF: 0.653

Gnomad AMR AF: 0.523

Gnomad ASJ AF: 0.608

Gnomad EAS AF: 0.224

Gnomad SAS AF: 0.541

Gnomad FIN AF: 0.602

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.632

Gnomad OTH AF: 0.518

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

GnomAD4 genome AF: 0.517 AC: 78306 AN: 151590 Hom.: 21750 Cov.: 0 AF XY: 0.513 AC XY: 37955 AN XY: 74004

Gnomad4 AFR AF: 0.327

Gnomad4 AMR AF: 0.522

Gnomad4 ASJ AF: 0.608

Gnomad4 EAS AF: 0.224

Gnomad4 SAS AF: 0.540

Gnomad4 FIN AF: 0.602

Gnomad4 NFE AF: 0.632

Gnomad4 OTH AF: 0.518

Alfa AF: 0.564 Hom.: 3071

Bravo AF: 0.500

Asia WGS AF: 0.385 AC: 1339 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs16416; hg19: chr15-25365169;