chr20-2467306-C-G

Variant names:

• chr20-2467306-C-G
• rs786201019
• NM_003091.4:c.155+301G>C

Variant summary

Our verdict is Likely pathogenic. The variant received 9 ACMG points: 10P and 1B. PM2 PP5_Very_Strong BP4

The NM_003091.4(SNRPB):​c.155+301G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SNRPB NM_003091.4 intron
• Clinical Significance: Pathogenic/Likely pathogenic criteria provided, multiple submitters, no conflicts P:9
• Conservation: PhyloP100: 0.728
• Publications: 3 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: Likely_pathogenic. The variant received 9 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 20-2467306-C-G is Pathogenic according to our data. Variant chr20-2467306-C-G is described in ClinVar as Pathogenic/Likely_pathogenic. ClinVar VariationId is 183431.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27). . 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+301G>C		intron	N/A	NP_003082.1	Q66K91
	SNRPB	NM_198216.2		c.155+301G>C		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+301G>C		intron	N/A	ENSP00000370746.3	P14678-2
	SNRPB	ENST00000438552.6	TSL:1	c.155+301G>C		intron	N/A	ENSP00000412566.2	P14678-1
	ENSG00000256566	ENST00000461548.1	TSL:5	n.*124G>C		non_coding_transcript_exon	Exon 7 of 7	ENSP00000456213.1	F5H5K5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Pathogenic/Likely pathogenic

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
7	-	-	Cerebro-costo-mandibular syndrome (7)
1	-	-	not provided (1)
1	-	-	SNRPB-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_noAF	Benign	-0.27
CADD	Benign	22
DANN	Benign	0.95
PhyloP100		0.73
Mutation Taster		=171/129	disease causing (ClinVar)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs786201019; hg19: chr20-2447952;