rs7514863

Variant names:

• chr1-211310758-A-T
• rs7514863
• NM_001136223.3:c.1076-1962A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001136223.3(RCOR3):​c.1076-1962A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 152,114 control chromosomes in the GnomAD database, including 2,866 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 0.18 (2866 hom., cov: 32)
• Consequence: RCOR3 NM_001136223.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.459
• Publications: 11 publications found

Genes affected

RCOR3 (HGNC:25594): (REST corepressor 3) Predicted to enable enzyme binding activity and transcription corepressor activity. Predicted to be involved in histone deacetylation; negative regulation of transcription, DNA-templated; and regulation of transcription by RNA polymerase II. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.279 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RCOR3	NM_001136223.3	c.1076-1962A>T		intron_variant	Intron 10 of 11	ENST00000419091.7	NP_001129695.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RCOR3	ENST00000419091.7	c.1076-1962A>T		intron_variant	Intron 10 of 11	2	NM_001136223.3	ENSP00000413929.2

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27837 AN: 151996 Hom.: 2864 Cov.: 32

Gnomad AFR AF: 0.284

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.0597

Gnomad SAS AF: 0.158

Gnomad FIN AF: 0.0985

Gnomad MID AF: 0.162

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.174

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.183 AC: 27864 AN: 152114 Hom.: 2866 Cov.: 32 AF XY: 0.182 AC XY: 13509 AN XY: 74396

African (AFR) AF: 0.284 AC: 11760 AN: 41458

American (AMR) AF: 0.174 AC: 2662 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.156 AC: 540 AN: 3472

East Asian (EAS) AF: 0.0594 AC: 308 AN: 5184

South Asian (SAS) AF: 0.158 AC: 760 AN: 4816

European-Finnish (FIN) AF: 0.0985 AC: 1044 AN: 10598

Middle Eastern (MID) AF: 0.168 AC: 49 AN: 292

European-Non Finnish (NFE) AF: 0.150 AC: 10212 AN: 67986

Other (OTH) AF: 0.172 AC: 364 AN: 2114

Alfa AF: 0.169 Hom.: 302

Bravo AF: 0.190

Asia WGS AF: 0.119 AC: 414 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	11
DANN	Benign	0.84
PhyloP100		0.46
Mutation Taster		=100/0	polymorphism (auto)

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: rs7514863; hg19: chr1-211484100;