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3-133807811-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_001379313.1(SRPRB):c.315C>T(p.Val105=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00244 in 1,609,990 control chromosomes in the GnomAD database, including 82 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.013 ( 47 hom., cov: 32)
Exomes 𝑓: 0.0014 ( 35 hom. )

Consequence

SRPRB
NM_001379313.1 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.05
Variant links:
Genes affected
SRPRB (HGNC:24085): (SRP receptor subunit beta) The protein encoded by this gene has similarity to mouse protein which is a subunit of the signal recognition particle receptor (SR). This subunit is a transmembrane GTPase belonging to the GTPase superfamily. It anchors alpha subunit, a peripheral membrane GTPase, to the ER membrane. SR is required for the cotranslational targeting of both secretory and membrane proteins to the ER membrane. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 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=-0.3).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 3-133807811-C-T is Benign according to our data. Variant chr3-133807811-C-T is described in ClinVar as [Benign]. Clinvar id is 785065.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=1.05 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0126 (1915/152198) while in subpopulation AFR AF= 0.0433 (1798/41514). AF 95% confidence interval is 0.0416. There are 47 homozygotes in gnomad4. There are 879 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 48 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SRPRBNM_001379313.1 linkuse as main transcriptc.315C>T p.Val105= synonymous_variant 3/7 ENST00000678299.1
SRPRBNM_021203.4 linkuse as main transcriptc.315C>T p.Val105= synonymous_variant 4/8
SRPRBNR_163491.1 linkuse as main transcriptn.349C>T non_coding_transcript_exon_variant 3/8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SRPRBENST00000678299.1 linkuse as main transcriptc.315C>T p.Val105= synonymous_variant 3/7 NM_001379313.1 P1
SRPRBENST00000466490.7 linkuse as main transcriptc.315C>T p.Val105= synonymous_variant 4/85 P1
SRPRBENST00000494297.5 linkuse as main transcriptn.217C>T non_coding_transcript_exon_variant 2/62
SRPRBENST00000484684.1 linkuse as main transcript downstream_gene_variant 2

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0126
AC:
1912
AN:
152080
Hom.:
48
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0433
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00498
Gnomad ASJ
AF:
0.000577
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000353
Gnomad OTH
AF:
0.00718
GnomAD3 exomes
AF:
0.00324
AC:
800
AN:
247202
Hom.:
16
AF XY:
0.00225
AC XY:
301
AN XY:
133780
show subpopulations
Gnomad AFR exome
AF:
0.0421
Gnomad AMR exome
AF:
0.00231
Gnomad ASJ exome
AF:
0.000399
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000102
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000239
Gnomad OTH exome
AF:
0.00182
GnomAD4 exome
AF:
0.00138
AC:
2008
AN:
1457792
Hom.:
35
Cov.:
29
AF XY:
0.00116
AC XY:
840
AN XY:
725318
show subpopulations
Gnomad4 AFR exome
AF:
0.0460
Gnomad4 AMR exome
AF:
0.00291
Gnomad4 ASJ exome
AF:
0.000728
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000152
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000927
Gnomad4 OTH exome
AF:
0.00330
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0126
AC:
1915
AN:
152198
Hom.:
47
Cov.:
32
AF XY:
0.0118
AC XY:
879
AN XY:
74414
show subpopulations
Gnomad4 AFR
AF:
0.0433
Gnomad4 AMR
AF:
0.00497
Gnomad4 ASJ
AF:
0.000577
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000353
Gnomad4 OTH
AF:
0.00711
Alfa
AF:
0.00424
Hom.:
9
Bravo
AF:
0.0151
Asia WGS
AF:
0.00202
AC:
7
AN:
3478
EpiCase
AF:
0.000327
EpiControl
AF:
0.000238

ClinVar

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

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.30
Cadd
Benign
13
Dann
Benign
0.84
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs112398870; hg19: chr3-133526655; API