Genetic Variant REDIC1:p.Arg191Cys (chr12-39650239-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001031748.4(REDIC1):c.571C>T(p.Arg191Cys) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000164 in 1,589,588 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

REDIC1
NM_001031748.4 missense, splice_region

Scores

Splicing: ADA: 0.0007403

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.143

Publications

5 publications found

Variant links:

Genes affected

REDIC1 (HGNC:26846): (regulator of DNA class I crossover intermediates 1)

REDIC1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.024488032).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001031748.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
REDIC1	NM_001031748.4	MANE Select	c.571C>T	p.Arg191Cys	missense splice_region	Exon 7 of 13	NP_001026918.2	Q86WS4-1
REDIC1	NM_001319247.2		c.571C>T	p.Arg191Cys	missense splice_region	Exon 7 of 11	NP_001306176.1	Q86WS4-2
REDIC1	NR_135051.2		n.586C>T		splice_region non_coding_transcript_exon	Exon 6 of 19

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
REDIC1	ENST00000324616.9	TSL:1 MANE Select	c.571C>T	p.Arg191Cys	missense splice_region	Exon 7 of 13	ENSP00000317671.5	Q86WS4-1
REDIC1	ENST00000405531.7	TSL:1	c.571C>T	p.Arg191Cys	missense splice_region	Exon 7 of 11	ENSP00000383897.3	Q86WS4-2
REDIC1	ENST00000468200.2	TSL:1	n.340C>T		splice_region non_coding_transcript_exon	Exon 6 of 19	ENSP00000473371.1	Q86WS4-3

Frequencies

GnomAD3 genomes

AF:

0.0000266

AC:

AN:

150658

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000661

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000209

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000295

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000302

AC:

AN:

231676

AF XY:

0.0000238

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000985

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000474

Gnomad NFE exome

AF:

0.0000187

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000153

AC:

AN:

1438818

Hom.:

Cov.:

AF XY:

0.0000182

AC XY:

AN XY:

715330

show subpopulations

African (AFR)

AF:

0.0000311

AC:

AN:

32148

American (AMR)

AF:

0.0000745

AC:

AN:

40268

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25410

East Asian (EAS)

AF:

0.00

AC:

AN:

39046

South Asian (SAS)

AF:

0.0000490

AC:

AN:

81638

European-Finnish (FIN)

AF:

0.0000190

AC:

AN:

52734

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5440

European-Non Finnish (NFE)

AF:

0.0000109

AC:

AN:

1102826

Other (OTH)

AF:

0.0000169

AC:

AN:

59308

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

AF:

0.0000265

AC:

AN:

150770

Hom.:

Cov.:

AF XY:

0.0000272

AC XY:

AN XY:

73566

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41114

American (AMR)

AF:

0.0000660

AC:

AN:

15146

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3454

East Asian (EAS)

AF:

0.00

AC:

AN:

5138

South Asian (SAS)

AF:

0.000209

AC:

AN:

4780

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10152

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000295

AC:

AN:

67694

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000414

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.0023

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.033

LIST_S2

Benign

0.43

M_CAP

Benign

0.0073

MetaRNN

Benign

0.024

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

-0.14

PROVEAN

Benign

-0.47

REVEL

Benign

0.040

Sift

Uncertain

0.023

Sift4G

Uncertain

0.010

Polyphen

0.10

Vest4

0.12

MutPred

0.27

Loss of solvent accessibility (P = 0.0079)

MVP

0.18

MPC

0.018

ClinPred

0.049

GERP RS

2.6

Varity_R

0.080

gMVP

0.030

Mutation Taster

=92/8

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00074

dbscSNV1_RF

Benign

0.070

SpliceAI score (max)

0.15

Details are displayed if max score is > 0.2

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

Publications

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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