chr20-2467305-C-A

Variant names:

• chr20-2467305-C-A
• rs786201020
• NM_003091.4:c.155+302G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 3P and 1B. PM2 PP5 BP4

The NM_003091.4(SNRPB):​c.155+302G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000581 in 516,262 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: SNRPB NM_003091.4 intron
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 3.38
• Publications: 1 publications found

Genes affected

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: G2P, Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, PanelApp Australia

ENSG00000256566 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 20-2467305-C-A is Pathogenic according to our data. Variant chr20-2467305-C-A is described in ClinVar as Pathogenic. ClinVar VariationId is 183433.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.25). . Strength limited to SUPPORTING due to the PP5.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003091.4. 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
	SNRPB	NM_003091.4	MANE Select	c.155+302G>T		intron	N/A	NP_003082.1	Q66K91
	SNRPB	NM_198216.2		c.155+302G>T		intron	N/A	NP_937859.1	P14678-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNRPB	ENST00000381342.7	TSL:1 MANE Select	c.155+302G>T		intron	N/A	ENSP00000370746.3	P14678-2
	SNRPB	ENST00000438552.6	TSL:1	c.155+302G>T		intron	N/A	ENSP00000412566.2	P14678-1
	ENSG00000256566	ENST00000461548.1	TSL:5	n.*125G>T		non_coding_transcript_exon	Exon 7 of 7	ENSP00000456213.1	F5H5K5

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152074 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000549 AC: 2 AN: 364188 Hom.: 0 Cov.: 0 AF XY: 0.00000492 AC XY: 1 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 AF: 0.00000658 AC: 1 AN: 152074 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74276

African (AFR) AF: 0.00 AC: 0 AN: 41400

American (AMR) AF: 0.0000655 AC: 1 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68010

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Cerebro-costo-mandibular syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	25
DANN	Benign	0.95
PhyloP100		3.4
Mutation Taster		=43/257	disease causing (ClinVar)

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;