NM_014781.5:c.3821+2750C>T

Variant names:

• chr8-52653258-G-A
• rs13250856
• NM_014781.5:c.3821+2750C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RB1CC1	NM_014781.5	c.3821+2750C>T		intron_variant	Intron 15 of 23	ENST00000025008.10	NP_055596.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RB1CC1	ENST00000025008.10	c.3821+2750C>T		intron_variant	Intron 15 of 23	1	NM_014781.5	ENSP00000025008.5
RB1CC1	ENST00000435644.6	c.3821+2750C>T		intron_variant	Intron 15 of 23	1		ENSP00000396067.2
RB1CC1	ENST00000521611.1	n.386-29787C>T		intron_variant	Intron 2 of 2	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

African (AFR) AF: 0.0578 AC: 2399 AN: 41508

American (AMR) AF: 0.282 AC: 4304 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.242 AC: 841 AN: 3472

East Asian (EAS) AF: 0.174 AC: 900 AN: 5158

South Asian (SAS) AF: 0.240 AC: 1158 AN: 4816

European-Finnish (FIN) AF: 0.333 AC: 3514 AN: 10552

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.324 AC: 22001 AN: 67950

Other (OTH) AF: 0.258 AC: 545 AN: 2112

Alfa AF: 0.286 Hom.: 3705

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
PhyloP100		-0.060
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: rs13250856; hg19: chr8-53565818;