NM_014781.5:c.72-591C>G

Variant names:

• chr8-52684604-G-C
• rs10504146
• NM_014781.5:c.72-591C>G

Variant summary

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

The NM_014781.5(RB1CC1):​c.72-591C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 152,078 control chromosomes in the GnomAD database, including 3,296 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 0.18 (3296 hom., cov: 33)
• Consequence: RB1CC1 NM_014781.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0880
• Publications: 1 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.632 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RB1CC1	NM_014781.5	c.72-591C>G		intron_variant	Intron 3 of 23	ENST00000025008.10	NP_055596.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RB1CC1	ENST00000025008.10	c.72-591C>G		intron_variant	Intron 3 of 23	1	NM_014781.5	ENSP00000025008.5

Frequencies

GnomAD3 genomes AF: 0.177 AC: 26931 AN: 151960 Hom.: 3291 Cov.: 33

Gnomad AFR AF: 0.0973

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.272

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.650

Gnomad SAS AF: 0.262

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.173

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

GnomAD4 genome AF: 0.177 AC: 26952 AN: 152078 Hom.: 3296 Cov.: 33 AF XY: 0.183 AC XY: 13608 AN XY: 74338

African (AFR) AF: 0.0974 AC: 4039 AN: 41478

American (AMR) AF: 0.273 AC: 4168 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 490 AN: 3470

East Asian (EAS) AF: 0.650 AC: 3365 AN: 5178

South Asian (SAS) AF: 0.262 AC: 1263 AN: 4820

European-Finnish (FIN) AF: 0.164 AC: 1733 AN: 10556

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.167 AC: 11346 AN: 67974

Other (OTH) AF: 0.172 AC: 364 AN: 2116

Alfa AF: 0.174 Hom.: 352

Bravo AF: 0.187

Asia WGS AF: 0.366 AC: 1267 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.8
DANN	Benign	0.58
PhyloP100		-0.088
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: rs10504146; hg19: chr8-53597164;