chr14-102592962-TCCG-T

Variant names:

• chr14-102592962-TCCG-T
• rs770589339
• NM_015156.4:c.88_90delGCC

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP3

The NM_015156.4(RCOR1):​c.88_90delGCC​(p.Ala30del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000141 in 1,164,832 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00016 (0 hom.)
• Consequence: RCOR1 NM_015156.4 conservative_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.04
• 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: Likely_benign. The variant received -1 ACMG points.

• 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.88_90delGCC	p.Ala30del	conservative_inframe_deletion	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.88_90delGCC	p.Ala30del	conservative_inframe_deletion	Exon 1 of 12	ENSP00000262241.5	Q9UKL0
	RCOR1	ENST00000908570.1		c.88_90delGCC	p.Ala30del	conservative_inframe_deletion	Exon 1 of 12	ENSP00000578629.1

Frequencies

GnomAD3 genomes AF: 0.0000204 AC: 3 AN: 146730 Hom.: 0 Cov.: 32

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: 0.00

Gnomad FIN AF: 0.000219

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000152

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00211 AC: 47 AN: 22264 AF XY: 0.00238

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00256

Gnomad ASJ exome AF: 0.00325

Gnomad EAS exome AF: 0.00373

Gnomad FIN exome AF: 0.00278

Gnomad NFE exome AF: 0.00177

Gnomad OTH exome AF: 0.00304

GnomAD4 exome AF: 0.000158 AC: 161 AN: 1018102 Hom.: 0 AF XY: 0.000206 AC XY: 101 AN XY: 491006

⚠️ 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: 19838

American (AMR) AF: 0.00105 AC: 9 AN: 8534

Ashkenazi Jewish (ASJ) AF: 0.000799 AC: 10 AN: 12512

East Asian (EAS) AF: 0.000192 AC: 3 AN: 15634

South Asian (SAS) AF: 0.00111 AC: 33 AN: 29662

European-Finnish (FIN) AF: 0.000713 AC: 12 AN: 16824

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2558

European-Non Finnish (NFE) AF: 0.0000960 AC: 84 AN: 874788

Other (OTH) AF: 0.000265 AC: 10 AN: 37752

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000204 AC: 3 AN: 146730 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 71504

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

African (AFR) AF: 0.00 AC: 0 AN: 40516

American (AMR) AF: 0.00 AC: 0 AN: 14806

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3384

East Asian (EAS) AF: 0.00 AC: 0 AN: 5084

South Asian (SAS) AF: 0.00 AC: 0 AN: 4780

European-Finnish (FIN) AF: 0.000219 AC: 2 AN: 9152

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 308

European-Non Finnish (NFE) AF: 0.0000152 AC: 1 AN: 65774

Other (OTH) AF: 0.00 AC: 0 AN: 2020

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.0
Mutation Taster		=79/21	polymorphism

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: rs770589339; hg19: chr14-103059299;