ENST00000461548.1:n.*125G>A

Variant names:

• chr20-2467305-C-T
• rs786201020
• ENST00000461548.1:n.*125G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000461548.1(ENSG00000256566):​n.*125G>A 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 0.00000549 in 364,188 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: ENSG00000256566 ENST00000461548.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.38
• Publications: 1 publications found

Genes affected

ENSG00000256566 (HGNC:):

SNRPB (HGNC:11153): (small nuclear ribonucleoprotein polypeptides B and B1) The protein encoded by this gene is one of several nuclear proteins that are found in common among U1, U2, U4/U6, and U5 small ribonucleoprotein particles (snRNPs). These snRNPs are involved in pre-mRNA splicing, and the encoded protein may also play a role in pre-mRNA splicing or snRNP structure. Autoantibodies from patients with systemic lupus erythematosus frequently recognize epitopes on the encoded protein. Two transcript variants encoding different isoforms (B and B') have been found for this gene. [provided by RefSeq, Jul 2008]

SNRPB Gene-Disease associations (from GenCC):

• cerebrocostomandibular syndrome

  Inheritance: AD, SD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet, G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.25).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNRPB	NM_003091.4	c.155+302G>A		intron_variant	Intron 2 of 6	ENST00000381342.7	NP_003082.1
SNRPB	NM_198216.2	c.155+302G>A		intron_variant	Intron 2 of 6		NP_937859.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000256566	ENST00000461548.1	n.*125G>A		non_coding_transcript_exon_variant	Exon 7 of 7	5		ENSP00000456213.1
ENSG00000256566	ENST00000461548.1	n.*125G>A		3_prime_UTR_variant	Exon 7 of 7	5		ENSP00000456213.1
SNRPB	ENST00000381342.7	c.155+302G>A		intron_variant	Intron 2 of 6	1	NM_003091.4	ENSP00000370746.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000549 AC: 2 AN: 364188 Hom.: 0 Cov.: 0 AF XY: 0.00000984 AC XY: 2 AN XY: 203340

African (AFR) AF: 0.00 AC: 0 AN: 10908

American (AMR) AF: 0.00 AC: 0 AN: 28976

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13460

East Asian (EAS) AF: 0.00 AC: 0 AN: 14628

South Asian (SAS) AF: 0.00 AC: 0 AN: 60288

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 16300

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3048

European-Non Finnish (NFE) AF: 0.00000505 AC: 1 AN: 198214

Other (OTH) AF: 0.0000544 AC: 1 AN: 18366

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	25
DANN	Benign	0.95
PhyloP100		3.4

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs786201020; hg19: chr20-2447951;