14-102592962-TCCGCCGCCG-TCCGCCGCCGCCGCCGCCG

Variant names:

• chr14-102592962-T-TCCGCCGCCG
• rs770589339
• NM_015156.4:c.82_90dupGCCGCCGCC

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP3

The NM_015156.4(RCOR1):​c.82_90dupGCCGCCGCC​(p.Ala28_Ala30dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000196 in 1,019,268 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S31S) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000020 (0 hom.)
• Consequence: RCOR1 NM_015156.4 conservative_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.608
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP3: Nonframeshift variant in repetitive region in NM_015156.4

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015156.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RCOR1	NM_015156.4	MANE Select	c.82_90dupGCCGCCGCC	p.Ala28_Ala30dup	conservative_inframe_insertion	Exon 1 of 12	NP_055971.2	Q9UKL0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RCOR1	ENST00000262241.7	TSL:1 MANE Select	c.82_90dupGCCGCCGCC	p.Ala28_Ala30dup	conservative_inframe_insertion	Exon 1 of 12	ENSP00000262241.5	Q9UKL0
	RCOR1	ENST00000908570.1		c.82_90dupGCCGCCGCC	p.Ala28_Ala30dup	conservative_inframe_insertion	Exon 1 of 12	ENSP00000578629.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000196 AC: 2 AN: 1019268 Hom.: 0 Cov.: 32 AF XY: 0.00000407 AC XY: 2 AN XY: 491696

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 19844

American (AMR) AF: 0.00 AC: 0 AN: 8576

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12538

East Asian (EAS) AF: 0.00 AC: 0 AN: 15662

South Asian (SAS) AF: 0.00 AC: 0 AN: 29810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 16890

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2562

European-Non Finnish (NFE) AF: 0.00000228 AC: 2 AN: 875578

Other (OTH) AF: 0.00 AC: 0 AN: 37808

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000037155), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.61

Splicing

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

Other links and lift over

dbSNP: rs770589339; hg19: chr14-103059299;