14-102593246-G-C

Position:

• chr14-102593246-G-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_015156.4(RCOR1):​c.302-20G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000345 in 1,508,244 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000033 (1 hom.)
• Consequence: RCOR1 NM_015156.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0470

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 Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BS2: High AC in GnomAd4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RCOR1	NM_015156.4	c.302-20G>C		intron_variant		ENST00000262241.7	NP_055971.2
RCOR1	XM_047431148.1	c.302-20G>C		intron_variant			XP_047287104.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RCOR1	ENST00000262241.7	c.302-20G>C		intron_variant		1	NM_015156.4	ENSP00000262241.5

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152100 Hom.: 0 Cov.: 33

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: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000883

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.0000772 AC: 9 AN: 116644 Hom.: 0 AF XY: 0.0000904 AC XY: 6 AN XY: 66386

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000595

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000207

Gnomad OTH exome AF: 0.000354

GnomAD4 exome AF: 0.0000332 AC: 45 AN: 1356144 Hom.: 1 Cov.: 33 AF XY: 0.0000447 AC XY: 30 AN XY: 671060

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000357

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000328

Gnomad4 SAS exome AF: 0.000308

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000169

Gnomad4 OTH exome AF: 0.0000180

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152100 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74298

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000883

Gnomad4 OTH AF: 0.000478

Alfa AF: 0.0000540 Hom.: 0

Bravo AF: 0.0000302

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	11
DANN	Benign	0.52
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs758677599; hg19: chr14-103059583;