Menu
GeneBe

19-40757498-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_004596.5(SNRPA):c.240A>G(p.Lys80=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0907 in 1,609,030 control chromosomes in the GnomAD database, including 9,783 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.15 ( 2821 hom., cov: 30)
Exomes 𝑓: 0.084 ( 6962 hom. )

Consequence

SNRPA
NM_004596.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.93
Variant links:
Genes affected
SNRPA (HGNC:11151): (small nuclear ribonucleoprotein polypeptide A) The protein encoded by this gene associates with stem loop II of the U1 small nuclear ribonucleoprotein, which binds the 5' splice site of precursor mRNAs and is required for splicing. The encoded protein autoregulates itself by polyadenylation inhibition of its own pre-mRNA via dimerization and has been implicated in the coupling of splicing and polyadenylation. [provided by RefSeq, Oct 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.67).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 19-40757498-A-G is Benign according to our data. Variant chr19-40757498-A-G is described in ClinVar as [Benign]. Clinvar id is 3056710.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=1.93 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SNRPANM_004596.5 linkuse as main transcriptc.240A>G p.Lys80= synonymous_variant 2/6 ENST00000243563.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SNRPAENST00000243563.8 linkuse as main transcriptc.240A>G p.Lys80= synonymous_variant 2/61 NM_004596.5 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.154
AC:
23246
AN:
151420
Hom.:
2792
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.340
Gnomad AMI
AF:
0.0585
Gnomad AMR
AF:
0.0754
Gnomad ASJ
AF:
0.0566
Gnomad EAS
AF:
0.201
Gnomad SAS
AF:
0.0637
Gnomad FIN
AF:
0.133
Gnomad MID
AF:
0.104
Gnomad NFE
AF:
0.0716
Gnomad OTH
AF:
0.115
GnomAD3 exomes
AF:
0.101
AC:
24952
AN:
247650
Hom.:
1984
AF XY:
0.0953
AC XY:
12773
AN XY:
134010
show subpopulations
Gnomad AFR exome
AF:
0.346
Gnomad AMR exome
AF:
0.0488
Gnomad ASJ exome
AF:
0.0623
Gnomad EAS exome
AF:
0.208
Gnomad SAS exome
AF:
0.0547
Gnomad FIN exome
AF:
0.132
Gnomad NFE exome
AF:
0.0743
Gnomad OTH exome
AF:
0.0811
GnomAD4 exome
AF:
0.0841
AC:
122642
AN:
1457492
Hom.:
6962
Cov.:
31
AF XY:
0.0825
AC XY:
59816
AN XY:
724912
show subpopulations
Gnomad4 AFR exome
AF:
0.356
Gnomad4 AMR exome
AF:
0.0507
Gnomad4 ASJ exome
AF:
0.0620
Gnomad4 EAS exome
AF:
0.213
Gnomad4 SAS exome
AF:
0.0562
Gnomad4 FIN exome
AF:
0.129
Gnomad4 NFE exome
AF:
0.0726
Gnomad4 OTH exome
AF:
0.0976
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.154
AC:
23318
AN:
151538
Hom.:
2821
Cov.:
30
AF XY:
0.154
AC XY:
11359
AN XY:
73996
show subpopulations
Gnomad4 AFR
AF:
0.341
Gnomad4 AMR
AF:
0.0752
Gnomad4 ASJ
AF:
0.0566
Gnomad4 EAS
AF:
0.201
Gnomad4 SAS
AF:
0.0629
Gnomad4 FIN
AF:
0.133
Gnomad4 NFE
AF:
0.0716
Gnomad4 OTH
AF:
0.115
Alfa
AF:
0.0996
Hom.:
725
Bravo
AF:
0.158
Asia WGS
AF:
0.140
AC:
485
AN:
3478
EpiCase
AF:
0.0710
EpiControl
AF:
0.0689

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

SNRPA-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesOct 22, 2019This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.67
Cadd
Benign
13
Dann
Benign
0.25
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.070
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2230694; hg19: chr19-41263403; COSMIC: COSV54681348; API