2-96314375-C-T

Variant names:

• chr2-96314375-C-T
• rs4907310
• ENST00000652267.1:c.-205+6761G>A

Variant summary

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

The ENST00000652267.1(SNRNP200):​c.-205+6761G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 151,882 control chromosomes in the GnomAD database, including 8,099 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 0.32 (8099 hom., cov: 32)
• Consequence: SNRNP200 ENST00000652267.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• Publications: 3 publications found

Genes affected

SNRNP200 (HGNC:30859): (small nuclear ribonucleoprotein U5 subunit 200) Pre-mRNA splicing is catalyzed by the spliceosome, a complex of specialized RNA and protein subunits that removes introns from a transcribed pre-mRNA segment. The spliceosome consists of small nuclear RNA proteins (snRNPs) U1, U2, U4, U5 and U6, together with approximately 80 conserved proteins. U5 snRNP contains nine specific proteins. This gene encodes one of the U5 snRNP-specific proteins. This protein belongs to the DEXH-box family of putative RNA helicases. It is a core component of U4/U6-U5 snRNPs and appears to catalyze an ATP-dependent unwinding of U4/U6 RNA duplices. Mutations in this gene cause autosomal-dominant retinitis pigmentosa. Alternatively spliced transcript variants encoding different isoforms have been found, but the full-length nature of these variants has not been determined. [provided by RefSeq, Mar 2010]

SNRNP200 Gene-Disease associations (from GenCC):

• SNRNP200-related dominant retinopathy

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• retinitis pigmentosa 33

  Inheritance: AR, AD Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000230747 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.672 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000652267.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNRNP200	ENST00000652267.1		c.-205+6761G>A		intron	N/A	ENSP00000498933.1	A0A494C1A5
	ENSG00000230747	ENST00000421534.1	TSL:3	n.596+6761G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47833 AN: 151762 Hom.: 8075 Cov.: 32

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.327

Gnomad ASJ AF: 0.415

Gnomad EAS AF: 0.246

Gnomad SAS AF: 0.691

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.417

Gnomad NFE AF: 0.324

Gnomad OTH AF: 0.346

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

GnomAD4 genome AF: 0.315 AC: 47900 AN: 151882 Hom.: 8099 Cov.: 32 AF XY: 0.318 AC XY: 23563 AN XY: 74200

African (AFR) AF: 0.275 AC: 11376 AN: 41392

American (AMR) AF: 0.326 AC: 4975 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.415 AC: 1439 AN: 3464

East Asian (EAS) AF: 0.247 AC: 1270 AN: 5146

South Asian (SAS) AF: 0.692 AC: 3337 AN: 4824

European-Finnish (FIN) AF: 0.224 AC: 2356 AN: 10540

Middle Eastern (MID) AF: 0.428 AC: 125 AN: 292

European-Non Finnish (NFE) AF: 0.324 AC: 22051 AN: 67956

Other (OTH) AF: 0.352 AC: 745 AN: 2114

Alfa AF: 0.310 Hom.: 1238

Bravo AF: 0.310

Asia WGS AF: 0.512 AC: 1778 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.3
DANN	Benign	0.64
PhyloP100		-1.0

Splicing

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

Other links and lift over

dbSNP: rs4907310; hg19: chr2-96980113;