rs6138178

Variant names:

• chr20-2467941-G-T
• rs6138178
• NM_003091.4:c.4-183C>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003091.4(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 NM_003091.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.111
• Publications: 11 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: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
SNRPB	NM_003091.4	c.4-183C>A		intron_variant	Intron 1 of 6	ENST00000381342.7	NP_003082.1
SNRPB	NM_198216.2	c.4-183C>A		intron_variant	Intron 1 of 6		NP_937859.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNRPB	ENST00000381342.7	c.4-183C>A		intron_variant	Intron 1 of 6	1	NM_003091.4	ENSP00000370746.3
ENSG00000256566	ENST00000461548.1	n.305-183C>A		intron_variant	Intron 5 of 6	5		ENSP00000456213.1

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

African (AFR) AF: 0.334 AC: 13840 AN: 41434

American (AMR) AF: 0.695 AC: 10629 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.734 AC: 2548 AN: 3470

East Asian (EAS) AF: 0.709 AC: 3668 AN: 5170

South Asian (SAS) AF: 0.603 AC: 2908 AN: 4820

European-Finnish (FIN) AF: 0.655 AC: 6887 AN: 10520

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.744 AC: 50546 AN: 67956

Other (OTH) AF: 0.649 AC: 1366 AN: 2104

Alfa AF: 0.672 Hom.: 11289

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 15, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	17
DANN	Benign	0.77
PhyloP100		0.11
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6138178; hg19: chr20-2448587;