rs691

Variant names:

• chr15-25119648-C-T
• rs691
• ENST00000626200.3:n.969C>T

Variant summary

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

The ENST00000626200.3(SNHG14):​n.969C>T 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 0.417 in 151,872 control chromosomes in the GnomAD database, including 13,502 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 0.42 (13502 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SNHG14 ENST00000626200.3 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.23
• Publications: 20 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]

IPW (HGNC:6109): (imprinted in Prader-Willi syndrome) This gene is non-protein coding, is expressed exclusively from the paternal allele, and may play a role in the imprinting process. Mutations in this gene are associated with Prader-Willi syndrome. [provided by RefSeq, May 2010]

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 (EAS) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000626200.3. 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
	IPW	NR_023915.1		n.1670C>T		non_coding_transcript_exon	Exon 3 of 3
	SNHG14	NR_146177.1		n.10396+1266C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNHG14	ENST00000626200.3	TSL:1	n.969C>T		non_coding_transcript_exon	Exon 5 of 5
	SNHG14	ENST00000549804.7	TSL:5	n.5016C>T		non_coding_transcript_exon	Exon 33 of 33
	SNHG14	ENST00000640631.2	TSL:5	n.12290C>T		non_coding_transcript_exon	Exon 38 of 38

Frequencies

GnomAD3 genomes AF: 0.417 AC: 63314 AN: 151754 Hom.: 13484 Cov.: 32

Gnomad AFR AF: 0.401

Gnomad AMI AF: 0.494

Gnomad AMR AF: 0.512

Gnomad ASJ AF: 0.473

Gnomad EAS AF: 0.536

Gnomad SAS AF: 0.418

Gnomad FIN AF: 0.364

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.402

Gnomad OTH AF: 0.415

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

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) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.417 AC: 63357 AN: 151872 Hom.: 13502 Cov.: 32 AF XY: 0.420 AC XY: 31138 AN XY: 74208

African (AFR) AF: 0.401 AC: 16605 AN: 41426

American (AMR) AF: 0.513 AC: 7826 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.473 AC: 1641 AN: 3466

East Asian (EAS) AF: 0.536 AC: 2750 AN: 5134

South Asian (SAS) AF: 0.419 AC: 2021 AN: 4824

European-Finnish (FIN) AF: 0.364 AC: 3840 AN: 10546

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.402 AC: 27272 AN: 67914

Other (OTH) AF: 0.417 AC: 878 AN: 2108

Alfa AF: 0.416 Hom.: 25483

Bravo AF: 0.432

Asia WGS AF: 0.484 AC: 1682 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	5.3
DANN	Benign	0.61
PhyloP100		1.2

Splicing

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

Other links and lift over

dbSNP: rs691; hg19: chr15-25364795;