chr14-102592979-C-A

Variant names:

• chr14-102592979-C-A
• rs569399655
• NM_015156.4:c.93C>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_015156.4(RCOR1):​c.93C>A​(p.Ser31Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000676 in 148,034 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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: 𝑓 0.0000068 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RCOR1 NM_015156.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.473
• Publications: 2 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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP7: Synonymous conserved (PhyloP=-0.473 with no splicing effect.

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.93C>A	p.Ser31Ser	synonymous	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.93C>A	p.Ser31Ser	synonymous	Exon 1 of 12	ENSP00000262241.5	Q9UKL0
	RCOR1	ENST00000908570.1		c.93C>A	p.Ser31Ser	synonymous	Exon 1 of 12	ENSP00000578629.1

Frequencies

GnomAD3 genomes AF: 0.00000676 AC: 1 AN: 148034 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 Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1011406 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 486264

African (AFR) AF: 0.00 AC: 0 AN: 19620

American (AMR) AF: 0.00 AC: 0 AN: 7242

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11346

East Asian (EAS) AF: 0.00 AC: 0 AN: 15352

South Asian (SAS) AF: 0.00 AC: 0 AN: 26616

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 16826

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2506

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 874506

Other (OTH) AF: 0.00 AC: 0 AN: 37392

GnomAD4 genome AF: 0.00000676 AC: 1 AN: 148034 Hom.: 0 Cov.: 33 AF XY: 0.0000139 AC XY: 1 AN XY: 72114

African (AFR) AF: 0.0000244 AC: 1 AN: 40930

American (AMR) AF: 0.00 AC: 0 AN: 14908

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3404

East Asian (EAS) AF: 0.00 AC: 0 AN: 5156

South Asian (SAS) AF: 0.00 AC: 0 AN: 4808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9178

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66390

Other (OTH) AF: 0.00 AC: 0 AN: 2038

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	7.2
DANN	Benign	0.76
PhyloP100		-0.47
PromoterAI		-0.029	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.6

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: rs569399655; hg19: chr14-103059316;