chr13-48453505-G-A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_000321.3(RB1):​c.1814+394G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0168 in 152,310 control chromosomes in the GnomAD database, including 48 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.017 ( 48 hom., cov: 32)

Consequence

RB1
NM_000321.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.76
Variant links:
Genes affected
RB1 (HGNC:9884): (RB transcriptional corepressor 1) The protein encoded by this gene is a negative regulator of the cell cycle and was the first tumor suppressor gene found. The encoded protein also stabilizes constitutive heterochromatin to maintain the overall chromatin structure. The active, hypophosphorylated form of the protein binds transcription factor E2F1. Defects in this gene are a cause of childhood cancer retinoblastoma (RB), bladder cancer, and osteogenic sarcoma. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.76).
BS1
Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0168 (2560/152310) while in subpopulation AMR AF = 0.0436 (666/15292). AF 95% confidence interval is 0.0408. There are 48 homozygotes in GnomAd4. There are 1245 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position FAILED quality control check.
BS2
High AC in GnomAd4 at 2560 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RB1NM_000321.3 linkc.1814+394G>A intron_variant Intron 18 of 26 ENST00000267163.6 NP_000312.2 P06400A0A024RDV3
RB1NM_001407165.1 linkc.1814+394G>A intron_variant Intron 18 of 26 NP_001394094.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RB1ENST00000267163.6 linkc.1814+394G>A intron_variant Intron 18 of 26 1 NM_000321.3 ENSP00000267163.4 P06400
RB1ENST00000650461.1 linkc.1814+394G>A intron_variant Intron 18 of 26 ENSP00000497193.1 A0A3B3IS71
RB1ENST00000643064.1 linkc.192+72062G>A intron_variant Intron 1 of 1 ENSP00000496005.1 A0A2R8Y743
RB1ENST00000480491.1 linkn.513+394G>A intron_variant Intron 2 of 2 5

Frequencies

GnomAD3 genomes
AF:
0.0168
AC:
2559
AN:
152192
Hom.:
48
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00473
Gnomad AMI
AF:
0.00219
Gnomad AMR
AF:
0.0434
Gnomad ASJ
AF:
0.0101
Gnomad EAS
AF:
0.000385
Gnomad SAS
AF:
0.00849
Gnomad FIN
AF:
0.0148
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0212
Gnomad OTH
AF:
0.0110
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0168
AC:
2560
AN:
152310
Hom.:
48
Cov.:
32
AF XY:
0.0167
AC XY:
1245
AN XY:
74474
show subpopulations
Gnomad4 AFR
AF:
0.00471
AC:
0.00471449
AN:
0.00471449
Gnomad4 AMR
AF:
0.0436
AC:
0.0435522
AN:
0.0435522
Gnomad4 ASJ
AF:
0.0101
AC:
0.0100865
AN:
0.0100865
Gnomad4 EAS
AF:
0.000386
AC:
0.000385505
AN:
0.000385505
Gnomad4 SAS
AF:
0.00829
AC:
0.008285
AN:
0.008285
Gnomad4 FIN
AF:
0.0148
AC:
0.0147834
AN:
0.0147834
Gnomad4 NFE
AF:
0.0212
AC:
0.0211562
AN:
0.0211562
Gnomad4 OTH
AF:
0.0109
AC:
0.0108798
AN:
0.0108798
Heterozygous variant carriers
0
133
266
399
532
665
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Genome Het
Genome Hom
Variant carriers
0
28
56
84
112
140
<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:
0.0197
Hom.:
19
Bravo
AF:
0.0180
Asia WGS
AF:
0.00577
AC:
20
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.76
CADD
Benign
11
DANN
Benign
0.64
Mutation Taster
=100/0
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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: rs4151580; hg19: chr13-49027641; API