20-17616724-G-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001365613.2(RRBP1):​c.3867+8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00419 in 1,594,136 control chromosomes in the GnomAD database, including 231 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 123 hom., cov: 34)
Exomes 𝑓: 0.0023 ( 108 hom. )

Consequence

RRBP1
NM_001365613.2 splice_region, intron

Scores

2
Splicing: ADA: 0.0003269
2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0840
Variant links:
Genes affected
RRBP1 (HGNC:10448): (ribosome binding protein 1) This gene encodes a ribosome-binding protein of the endoplasmic reticulum (ER) membrane. Studies suggest that this gene plays a role in ER proliferation, secretory pathways and secretory cell differentiation, and mediation of ER-microtubule interactions. Alternative splicing has been observed and protein isoforms are characterized by regions of N-terminal decapeptide and C-terminal heptad repeats. Splicing of the tandem repeats results in variations in ribosome-binding affinity and secretory function. The full-length nature of variants which differ in repeat length has not been determined. Pseudogenes of this gene have been identified on chromosomes 3 and 7, and RRBP1 has been excluded as a candidate gene in the cause of Alagille syndrome, the result of a mutation in a nearby gene on chromosome 20p12. [provided by RefSeq, Apr 2012]

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.69).
BP6
Variant 20-17616724-G-A is Benign according to our data. Variant chr20-17616724-G-A is described in ClinVar as [Benign]. Clinvar id is 781544.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0747 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RRBP1NM_001365613.2 linkc.3867+8C>T splice_region_variant, intron_variant Intron 21 of 24 ENST00000377813.6 NP_001352542.1
RRBP1NM_001042576.2 linkc.2568+8C>T splice_region_variant, intron_variant Intron 22 of 25 NP_001036041.2 Q9P2E9-3
RRBP1NM_004587.3 linkc.2568+8C>T splice_region_variant, intron_variant Intron 21 of 24 NP_004578.3 Q9P2E9-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RRBP1ENST00000377813.6 linkc.3867+8C>T splice_region_variant, intron_variant Intron 21 of 24 1 NM_001365613.2 ENSP00000367044.1 Q9P2E9-1

Frequencies

GnomAD3 genomes
AF:
0.0221
AC:
3366
AN:
152192
Hom.:
123
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.0770
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00752
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000323
Gnomad OTH
AF:
0.0172
GnomAD2 exomes
AF:
0.00599
AC:
1458
AN:
243554
AF XY:
0.00438
show subpopulations
Gnomad AFR exome
AF:
0.0803
Gnomad AMR exome
AF:
0.00390
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000244
Gnomad OTH exome
AF:
0.00254
GnomAD4 exome
AF:
0.00229
AC:
3304
AN:
1441826
Hom.:
108
Cov.:
30
AF XY:
0.00191
AC XY:
1372
AN XY:
718388
show subpopulations
Gnomad4 AFR exome
AF:
0.0781
AC:
2555
AN:
32726
Gnomad4 AMR exome
AF:
0.00403
AC:
174
AN:
43156
Gnomad4 ASJ exome
AF:
0.00
AC:
0
AN:
25800
Gnomad4 EAS exome
AF:
0.00
AC:
0
AN:
39398
Gnomad4 SAS exome
AF:
0.000199
AC:
17
AN:
85536
Gnomad4 FIN exome
AF:
0.0000194
AC:
1
AN:
51474
Gnomad4 NFE exome
AF:
0.000205
AC:
225
AN:
1098340
Gnomad4 Remaining exome
AF:
0.00533
AC:
318
AN:
59692
Heterozygous variant carriers
0
161
323
484
646
807
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Exome Het
Exome Hom
Variant carriers
0
80
160
240
320
400
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.0221
AC:
3371
AN:
152310
Hom.:
123
Cov.:
34
AF XY:
0.0204
AC XY:
1519
AN XY:
74454
show subpopulations
Gnomad4 AFR
AF:
0.0769
AC:
0.0769231
AN:
0.0769231
Gnomad4 AMR
AF:
0.00751
AC:
0.00751241
AN:
0.00751241
Gnomad4 ASJ
AF:
0.00
AC:
0
AN:
0
Gnomad4 EAS
AF:
0.00
AC:
0
AN:
0
Gnomad4 SAS
AF:
0.00
AC:
0
AN:
0
Gnomad4 FIN
AF:
0.00
AC:
0
AN:
0
Gnomad4 NFE
AF:
0.000323
AC:
0.000323415
AN:
0.000323415
Gnomad4 OTH
AF:
0.0170
AC:
0.0170132
AN:
0.0170132
Heterozygous variant carriers
0
147
294
442
589
736
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Genome Het
Genome Hom
Variant carriers
0
34
68
102
136
170
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.0101
Hom.:
17
Bravo
AF:
0.0250
Asia WGS
AF:
0.00433
AC:
16
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Dec 31, 2019
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

-
Breakthrough Genomics, Breakthrough Genomics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.69
CADD
Benign
3.7
DANN
Benign
0.58
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Mutation Taster
=97/3
polymorphism (auto)

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.00033
dbscSNV1_RF
Benign
0.0020
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

Publications

LitVar

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

Other links and lift over

dbSNP: rs56102376; hg19: chr20-17597369; API