chr15-25062942-C-T

Variant names:

• chr15-25062942-C-T
• rs965676
• ENST00000549804.7:n.397+854C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000549804.7(SNHG14):​n.397+854C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0633 in 152,208 control chromosomes in the GnomAD database, including 361 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 0.063 (361 hom., cov: 32)
• Consequence: SNHG14 ENST00000549804.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.76
• Publications: 1 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0932 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000549804.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNHG14	NR_146177.1		n.5904+854C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNHG14	ENST00000549804.7	TSL:5	n.397+854C>T		intron	N/A
	SNHG14	ENST00000640631.2	TSL:5	n.2178+854C>T		intron	N/A
	SNHG14	ENST00000654223.1		n.1532+854C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0633 AC: 9627 AN: 152090 Hom.: 362 Cov.: 32

Gnomad AFR AF: 0.0957

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.0537

Gnomad ASJ AF: 0.0329

Gnomad EAS AF: 0.00309

Gnomad SAS AF: 0.0193

Gnomad FIN AF: 0.0354

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0602

Gnomad OTH AF: 0.0627

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

GnomAD4 genome AF: 0.0633 AC: 9637 AN: 152208 Hom.: 361 Cov.: 32 AF XY: 0.0612 AC XY: 4555 AN XY: 74412

African (AFR) AF: 0.0956 AC: 3971 AN: 41520

American (AMR) AF: 0.0536 AC: 819 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0329 AC: 114 AN: 3466

East Asian (EAS) AF: 0.00309 AC: 16 AN: 5174

South Asian (SAS) AF: 0.0195 AC: 94 AN: 4824

European-Finnish (FIN) AF: 0.0354 AC: 375 AN: 10590

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0603 AC: 4099 AN: 68022

Other (OTH) AF: 0.0625 AC: 132 AN: 2112

Alfa AF: 0.0669 Hom.: 66

Bravo AF: 0.0684

Asia WGS AF: 0.0220 AC: 76 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.86
DANN	Benign	0.38
PhyloP100		-4.8

Splicing

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

Other links and lift over

dbSNP: rs965676; hg19: chr15-25308089;