chr14-102592956-T-TCCGCCTCCGCCGCCG

Position:

• chr14-102592956-T-TCCGCCTCCGCCGCCG

Variant summary

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

The ENST00000262241.7(RCOR1):​c.88_102dup​(p.Ala30_Ala34dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000426 in 1,174,192 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000034 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000044 (0 hom.)
• Consequence: RCOR1 ENST00000262241.7 inframe_insertion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.27

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 Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RCOR1	NM_015156.4	c.88_102dup	p.Ala30_Ala34dup	inframe_insertion	1/12	ENST00000262241.7	NP_055971.2
RCOR1	XM_047431148.1	c.88_102dup	p.Ala30_Ala34dup	inframe_insertion	1/10		XP_047287104.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RCOR1	ENST00000262241.7	c.88_102dup	p.Ala30_Ala34dup	inframe_insertion	1/12	1	NM_015156.4	ENSP00000262241	P1

Frequencies

GnomAD3 genomes AF: 0.0000341 AC: 5 AN: 146820 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000742

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000196

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000152

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000438 AC: 45 AN: 1027372 Hom.: 0 Cov.: 33 AF XY: 0.0000524 AC XY: 26 AN XY: 496372

Gnomad4 AFR exome AF: 0.0000500

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000323

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000454

Gnomad4 OTH exome AF: 0.0000786

GnomAD4 genome AF: 0.0000341 AC: 5 AN: 146820 Hom.: 0 Cov.: 33 AF XY: 0.0000280 AC XY: 2 AN XY: 71542

Gnomad4 AFR AF: 0.0000742

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000196

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000152

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 24, 2021

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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant has not been reported in the literature in individuals affected with RCOR1-related conditions. 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, c.88_102dup, results in the insertion of 5 amino acid(s) of the RCOR1 protein (p.Ala30_Ala34dup), but otherwise preserves the integrity of the reading frame. -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs769670360; hg19: chr14-103059293;