20-2470762-G-T

Variant names:

• chr20-2470762-G-T
• rs786201022
• NM_003091.4:c.-72C>A

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.-72C>A variant causes a 5 prime UTR 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 Pathogenic (no stars).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SNRPB NM_003091.4 5_prime_UTR
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: -2.02
• 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet, G2P

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 20-2470762-G-T is Pathogenic according to our data. Variant chr20-2470762-G-T is described in ClinVar as Pathogenic. ClinVar VariationId is 183435.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72). . 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.-72C>A		5_prime_UTR	Exon 1 of 7	NP_003082.1
	SNRPB	NM_198216.2		c.-72C>A		5_prime_UTR	Exon 1 of 7	NP_937859.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNRPB	ENST00000381342.7	TSL:1 MANE Select	c.-72C>A		5_prime_UTR	Exon 1 of 7	ENSP00000370746.3
	SNRPB	ENST00000438552.6	TSL:1	c.-72C>A		5_prime_UTR	Exon 1 of 7	ENSP00000412566.2
	ENSG00000256566	ENST00000461548.1	TSL:5	n.305-3004C>A		intron	N/A	ENSP00000456213.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 7.00e-7 AC: 1 AN: 1428248 Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0 AN XY: 712392

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 32890

American (AMR) AF: 0.00 AC: 0 AN: 44354

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25884

East Asian (EAS) AF: 0.00 AC: 0 AN: 39480

South Asian (SAS) AF: 0.00 AC: 0 AN: 85538

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48792

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5702

European-Non Finnish (NFE) AF: 9.20e-7 AC: 1 AN: 1086418

Other (OTH) AF: 0.00 AC: 0 AN: 59190

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions as Germline

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
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.95
DANN	Benign	0.87
PhyloP100		-2.0
PromoterAI		0.30	Neutral
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.1
Mutation Taster		=82/218	disease causing (ClinVar)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs786201022; hg19: chr20-2451408;