rs13250856

chr8-52653258-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014781.5(RB1CC1):c.3821+2750C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 152,044 control chromosomes in the GnomAD database, including 5,318 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 0.24 (5318 hom., cov: 31)
• Consequence: RB1CC1 NM_014781.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0600

Genes affected

RB1CC1 (HGNC:15574): (RB1 inducible coiled-coil 1) The protein encoded by this gene interacts with signaling pathways to coordinately regulate cell growth, cell proliferation, apoptosis, autophagy, and cell migration. This tumor suppressor also enhances retinoblastoma 1 gene expression in cancer cells. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Nov 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RB1CC1	NM_014781.5	c.3821+2750C>T		intron_variant		ENST00000025008.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RB1CC1	ENST00000025008.10	c.3821+2750C>T		intron_variant		1	NM_014781.5	P4
RB1CC1	ENST00000435644.6	c.3821+2750C>T		intron_variant		1		A1
RB1CC1	ENST00000521611.1	n.386-29787C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.237 AC: 36009 AN: 151926 Hom.: 5313 Cov.: 31

Gnomad AFR AF: 0.0579

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.242

Gnomad EAS AF: 0.175

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.333

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.324

Gnomad OTH AF: 0.256

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.237 AC: 36016 AN: 152044 Hom.: 5318 Cov.: 31 AF XY: 0.239 AC XY: 17718 AN XY: 74270

Gnomad4 AFR AF: 0.0578

Gnomad4 AMR AF: 0.282

Gnomad4 ASJ AF: 0.242

Gnomad4 EAS AF: 0.174

Gnomad4 SAS AF: 0.240

Gnomad4 FIN AF: 0.333

Gnomad4 NFE AF: 0.324

Gnomad4 OTH AF: 0.258

Alfa AF: 0.269 Hom.: 1267

Bravo AF: 0.227

Asia WGS AF: 0.253 AC: 883 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	3.5
Dann	Benign	0.26

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: rs13250856; hg19: chr8-53565818;