Genetic Variant RCOR1:p.Ala30dup (chr14-102592962-T-TCCG) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP3BS1_SupportingBS2

The NM_015156.4(RCOR1):c.88_90dupGCC(p.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 0.000983 in 1,166,100 control chromosomes in the GnomAD database, including 25 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. S31S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0012 ( 4 hom., cov: 33)

Exomes 𝑓: 0.00095 ( 21 hom. )

Consequence

RCOR1
NM_015156.4 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 0.608

Publications

0 publications found

Variant links:

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]

RCOR1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_015156.4

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00122 (179/146844) while in subpopulation SAS AF = 0.0333 (159/4776). AF 95% confidence interval is 0.0291. There are 4 homozygotes in GnomAd4. There are 132 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High AC in GnomAd4 at 179 AD gene.

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_90dupGCC	p.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.88_90dupGCC	p.Ala30dup	conservative_inframe_insertion	Exon 1 of 12	ENSP00000262241.5	Q9UKL0
	RCOR1	ENST00000908570.1		c.88_90dupGCC	p.Ala30dup	conservative_inframe_insertion	Exon 1 of 12	ENSP00000578629.1

Frequencies

GnomAD3 genomes

AF:

0.00123

AC:

180

AN:

146734

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000740

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000393

Gnomad SAS

AF:

0.0335

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000198

Gnomad OTH

AF:

0.000990

GnomAD2 exomes

AF:

0.00400

AC:

AN:

22264

AF XY:

0.00563

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000949

AC:

967

AN:

1019256

Hom.:

Cov.:

AF XY:

0.00119

AC XY:

585

AN XY:

491686

show subpopulations

African (AFR)

AF:

0.0000504

AC:

AN:

19844

American (AMR)

AF:

0.000233

AC:

AN:

8576

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12538

East Asian (EAS)

AF:

0.000830

AC:

AN:

15662

South Asian (SAS)

AF:

0.0250

AC:

746

AN:

29800

European-Finnish (FIN)

AF:

0.00

AC:

AN:

16890

Middle Eastern (MID)

AF:

0.00351

AC:

AN:

2562

European-Non Finnish (NFE)

AF:

0.000144

AC:

126

AN:

875576

Other (OTH)

AF:

0.00185

AC:

AN:

37808

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

128

170

213

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00122

AC:

179

AN:

146844

Hom.:

Cov.:

AF XY:

0.00184

AC XY:

132

AN XY:

71626

show subpopulations

African (AFR)

AF:

0.0000738

AC:

AN:

40632

American (AMR)

AF:

0.00

AC:

AN:

14826

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3384

East Asian (EAS)

AF:

0.000395

AC:

AN:

5068

South Asian (SAS)

AF:

0.0333

AC:

159

AN:

4776

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9156

Middle Eastern (MID)

AF:

0.00

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.000198

AC:

AN:

65764

Other (OTH)

AF:

0.000978

AC:

AN:

2044

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.61

Mutation Taster

=78/22

polymorphism

(source)

Splicing

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

Publications

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14-102592962-TCCGCCGCCG-TCCGCCGCCGCCG

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over