13-48317100-A-G

Position:

• chr13-48317100-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
RB1	NM_000321.3	c.264+9694A>G		intron_variant		ENST00000267163.6	NP_000312.2
RB1	NM_001407165.1	c.264+9694A>G		intron_variant			NP_001394094.1
RB1	NM_001407166.1	c.264+9694A>G		intron_variant			NP_001394095.1
RB1	NM_001407167.1	c.264+9694A>G		intron_variant			NP_001394096.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RB1	ENST00000267163.6	c.264+9694A>G		intron_variant		1	NM_000321.3	ENSP00000267163	P1
PPP1R26P1	ENST00000474415.1	n.3376T>C		non_coding_transcript_exon_variant	1/1

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

Gnomad4 AFR exome AF: 0.0477

Gnomad4 AMR exome AF: 0.138

Gnomad4 ASJ exome AF: 0.134

Gnomad4 EAS exome AF: 0.216

Gnomad4 SAS exome AF: 0.223

Gnomad4 FIN exome AF: 0.211

Gnomad4 NFE exome AF: 0.102

Gnomad4 OTH exome AF: 0.123

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

Gnomad4 AFR AF: 0.0849

Gnomad4 AMR AF: 0.138

Gnomad4 ASJ AF: 0.179

Gnomad4 EAS AF: 0.228

Gnomad4 SAS AF: 0.265

Gnomad4 FIN AF: 0.221

Gnomad4 NFE AF: 0.187

Gnomad4 OTH AF: 0.149

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

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

Other links and lift over

dbSNP: rs2854345; hg19: chr13-48891236;