Variant 14-102593066-A-AGCC details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_015156.4(RCOR1):c.190_192dupGCC(p.Ala64dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000478 in 1,401,970 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000051 ( 0 hom. )

Consequence

RCOR1
NM_015156.4 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.44

Variant links:

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]

RCOR1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 64 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RCOR1	NM_015156.4 link	c.190_192dupGCC	p.Ala64dup	conservative_inframe_insertion	Exon 1 of 12	ENST00000262241.7	NP_055971.2	Q9UKL0
RCOR1	XM_047431148.1 link	c.190_192dupGCC	p.Ala64dup	conservative_inframe_insertion	Exon 1 of 10		XP_047287104.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RCOR1	ENST00000262241.7 link	c.190_192dupGCC	p.Ala64dup	conservative_inframe_insertion	Exon 1 of 12	1	NM_015156.4	ENSP00000262241.5		Q9UKL0

Frequencies

GnomAD3 genomes

AF:

0.0000200

AC:

AN:

149666

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000210

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000297

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000586

AC:

AN:

68282

Hom.:

AF XY:

0.000100

AC XY:

AN XY:

39940

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000217

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000418

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000511

AC:

AN:

1252192

Hom.:

Cov.:

AF XY:

0.0000697

AC XY:

AN XY:

616618

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000356

Gnomad4 FIN exome

AF:

0.0000229

Gnomad4 NFE exome

AF:

0.0000389

Gnomad4 OTH exome

AF:

0.0000400

GnomAD4 genome

AF:

0.0000200

AC:

AN:

149778

Hom.:

Cov.:

AF XY:

0.0000137

AC XY:

AN XY:

73166

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000210

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000297

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Jan 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant, c.190_192dup, results in the insertion of 1 amino acid(s) of the RCOR1 protein (p.Ala64dup), but otherwise preserves the integrity of the reading frame. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with RCOR1-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over