rs877826

chr5-139283108-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NR_182754.1(SNHG4):n.1199T>G 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 0.5 in 152,226 control chromosomes in the GnomAD database, including 23,161 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 0.50 (23154 hom., cov: 33)
  • Exomes 𝑓: 0.66 (7 hom.)
• Consequence: SNHG4 NR_182754.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.498

Genes affected

SNHG4 (HGNC:32964): (small nucleolar RNA host gene 4)

LOC124901081 (HGNC:):

SIL1 (HGNC:24624): (SIL1 nucleotide exchange factor) This gene encodes a resident endoplasmic reticulum (ER), N-linked glycoprotein with an N-terminal ER targeting sequence, 2 putative N-glycosylation sites, and a C-terminal ER retention signal. This protein functions as a nucleotide exchange factor for another unfolded protein response protein. Mutations in this gene have been associated with Marinesco-Sjogren syndrome. Alternate transcriptional splice variants have been characterized. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.679 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNHG4	NR_182754.1	n.1199T>G		non_coding_transcript_exon_variant	6/6
LOC124901081	XR_007058956.1	n.347+2140A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNHG4	ENST00000505522.6	n.592T>G		non_coding_transcript_exon_variant	5/5	1
SNHG4	ENST00000507197.5	n.729T>G		non_coding_transcript_exon_variant	6/6	2
SIL1	ENST00000508744.1	n.347+2140A>C		intron_variant, non_coding_transcript_variant		4
SIL1	ENST00000509400.5	n.175+2140A>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.500 AC: 76085 AN: 152070 Hom.: 23160 Cov.: 33

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.576

Gnomad AMR AF: 0.557

Gnomad ASJ AF: 0.612

Gnomad EAS AF: 0.197

Gnomad SAS AF: 0.612

Gnomad FIN AF: 0.618

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.684

Gnomad OTH AF: 0.533

GnomAD4 exome AF: 0.658 AC: 25 AN: 38 Hom.: 7 Cov.: 0 AF XY: 0.615 AC XY: 16 AN XY: 26

Gnomad4 AFR exome AF: 0.00

Gnomad4 NFE exome AF: 0.719

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.500 AC: 76082 AN: 152188 Hom.: 23154 Cov.: 33 AF XY: 0.496 AC XY: 36892 AN XY: 74388

Gnomad4 AFR AF: 0.158

Gnomad4 AMR AF: 0.557

Gnomad4 ASJ AF: 0.612

Gnomad4 EAS AF: 0.197

Gnomad4 SAS AF: 0.611

Gnomad4 FIN AF: 0.618

Gnomad4 NFE AF: 0.684

Gnomad4 OTH AF: 0.532

Alfa AF: 0.606 Hom.: 6643

Bravo AF: 0.478

Asia WGS AF: 0.380 AC: 1324 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.5
Dann	Benign	0.50

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

Publications

LitVar

Other links and lift over

dbSNP: rs877826; hg19: chr5-138618797;