20-2467941-G-T

Position:

• chr20-2467941-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000381342.7(SNRPB):​c.4-183C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.613 in 151,964 control chromosomes in the GnomAD database, including 31,028 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.61 (31028 hom., cov: 32)
• Consequence: SNRPB ENST00000381342.7 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.111

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 20-2467941-G-T is Benign according to our data. Variant chr20-2467941-G-T is described in ClinVar as [Benign]. Clinvar id is 1274225.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.738 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNRPB	NM_003091.4	c.4-183C>A		intron_variant		ENST00000381342.7	NP_003082.1
SNRPB	NM_198216.2	c.4-183C>A		intron_variant			NP_937859.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNRPB	ENST00000381342.7	c.4-183C>A		intron_variant		1	NM_003091.4	ENSP00000370746	P1

Frequencies

GnomAD3 genomes AF: 0.614 AC: 93178 AN: 151844 Hom.: 31013 Cov.: 32

Gnomad AFR AF: 0.334

Gnomad AMI AF: 0.690

Gnomad AMR AF: 0.695

Gnomad ASJ AF: 0.734

Gnomad EAS AF: 0.710

Gnomad SAS AF: 0.601

Gnomad FIN AF: 0.655

Gnomad MID AF: 0.704

Gnomad NFE AF: 0.744

Gnomad OTH AF: 0.654

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

GnomAD4 genome AF: 0.613 AC: 93227 AN: 151964 Hom.: 31028 Cov.: 32 AF XY: 0.613 AC XY: 45551 AN XY: 74266

Gnomad4 AFR AF: 0.334

Gnomad4 AMR AF: 0.695

Gnomad4 ASJ AF: 0.734

Gnomad4 EAS AF: 0.709

Gnomad4 SAS AF: 0.603

Gnomad4 FIN AF: 0.655

Gnomad4 NFE AF: 0.744

Gnomad4 OTH AF: 0.649

Alfa AF: 0.662 Hom.: 5265

Bravo AF: 0.604

Asia WGS AF: 0.609 AC: 2122 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 15, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	17
DANN	Benign	0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs6138178; hg19: chr20-2448587;