rs753582127

Variant names:

• chr14-102592954-C-G
• rs753582127
• NM_015156.4:c.68C>G

Your query was ambiguous. Multiple possible variants found:

• chr14-102592954-C-G
• chr14-102592954-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015156.4(RCOR1):​c.68C>G​(p.Ala23Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000254 in 1,179,020 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000068 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000019 (0 hom.)
• Consequence: RCOR1 NM_015156.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.413

Genes affected

RCOR1 (HGNC:17441): (REST corepressor 1) This gene encodes a protein that is well-conserved, downregulated at birth, and with a specific role in determining neural cell differentiation. The encoded protein binds to the C-terminal domain of REST (repressor element-1 silencing transcription factor). [provided by RefSeq, Aug 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08283788).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RCOR1	NM_015156.4	c.68C>G	p.Ala23Gly	missense_variant	Exon 1 of 12	ENST00000262241.7	NP_055971.2
RCOR1	XM_047431148.1	c.68C>G	p.Ala23Gly	missense_variant	Exon 1 of 10		XP_047287104.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RCOR1	ENST00000262241.7	c.68C>G	p.Ala23Gly	missense_variant	Exon 1 of 12	1	NM_015156.4	ENSP00000262241.5

Frequencies

GnomAD3 genomes AF: 0.00000676 AC: 1 AN: 147842 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000244

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000194 AC: 2 AN: 1031178 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 498356

Gnomad4 AFR exome AF: 0.0000994

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00000676 AC: 1 AN: 147842 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 72078

Gnomad4 AFR AF: 0.0000244

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	16
DANN	Benign	0.79
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.083	T
MetaSVM	Benign	-1.0	T
PrimateAI	Pathogenic	0.81	D
REVEL	Benign	0.064
Sift4G	Benign	0.41	T
Vest4		0.075
MVP		0.17
MPC		0.64
ClinPred		0.090	T
GERP RS		0.65
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.6
Varity_R		0.030
gMVP		0.22

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: rs753582127; hg19: chr14-103059291;