13-48317100-A-G

Variant names:

• chr13-48317100-A-G
• rs2854345
• NM_000321.3:c.264+9694A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000321.3(RB1):​c.264+9694A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 865,556 control chromosomes in the GnomAD database, including 9,224 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 0.16 (2177 hom., cov: 33)
  • Exomes 𝑓: 0.12 (7047 hom.)
• Consequence: RB1 NM_000321.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.366
• Publications: 7 publications found

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]

PPP1R26P1 (HGNC:42015): (protein phosphatase 1 regulatory subunit 26 pseudogene 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.253 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RB1	NM_000321.3	c.264+9694A>G		intron_variant	Intron 2 of 26	ENST00000267163.6	NP_000312.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RB1	ENST00000267163.6	c.264+9694A>G		intron_variant	Intron 2 of 26	1	NM_000321.3	ENSP00000267163.4

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24320 AN: 152118 Hom.: 2182 Cov.: 33

Gnomad AFR AF: 0.0851

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.179

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.152

GnomAD4 exome AF: 0.116 AC: 82694 AN: 713320 Hom.: 7047 Cov.: 10 AF XY: 0.121 AC XY: 42731 AN XY: 351954

African (AFR) AF: 0.0477 AC: 792 AN: 16618

American (AMR) AF: 0.138 AC: 1972 AN: 14332

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 1383 AN: 10320

East Asian (EAS) AF: 0.216 AC: 4135 AN: 19118

South Asian (SAS) AF: 0.223 AC: 6719 AN: 30192

European-Finnish (FIN) AF: 0.211 AC: 7250 AN: 34388

Middle Eastern (MID) AF: 0.112 AC: 215 AN: 1926

European-Non Finnish (NFE) AF: 0.102 AC: 56675 AN: 557522

Other (OTH) AF: 0.123 AC: 3553 AN: 28904

GnomAD4 genome AF: 0.160 AC: 24313 AN: 152236 Hom.: 2177 Cov.: 33 AF XY: 0.165 AC XY: 12282 AN XY: 74430

African (AFR) AF: 0.0849 AC: 3529 AN: 41580

American (AMR) AF: 0.138 AC: 2118 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.179 AC: 621 AN: 3472

East Asian (EAS) AF: 0.228 AC: 1175 AN: 5160

South Asian (SAS) AF: 0.265 AC: 1278 AN: 4828

European-Finnish (FIN) AF: 0.221 AC: 2344 AN: 10600

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.187 AC: 12712 AN: 67974

Other (OTH) AF: 0.149 AC: 315 AN: 2112

Alfa AF: 0.177 Hom.: 317

Bravo AF: 0.150

Asia WGS AF: 0.233 AC: 809 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	13
DANN	Benign	0.80
PhyloP100		0.37
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2854345; hg19: chr13-48891236;