Genetic Variant LINC00632:n.1016C>T (chrX-140783739-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NR_173139.1(LINC00632):n.909C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000438 in 1,209,135 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 9 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000090 ( 0 hom., 2 hem., cov: 24)

Exomes 𝑓: 0.000039 ( 0 hom. 7 hem. )

Consequence

LINC00632
NR_173139.1 non_coding_transcript_exon

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.22

Publications

7 publications found

Variant links:

Genes affected

LINC00632 (HGNC:27865): (long intergenic non-protein coding RNA 632)

LINC00632 links:

CDR1 (HGNC:1798): (cerebellar degeneration related 1)

CDR1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.14453644).

BS2

High Hemizygotes in GnomAd4 at 2 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NR_173139.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
LINC00632	NR_173140.2	MANE Select	n.1016C>T	non_coding_transcript_exon	Exon 5 of 5
LINC00632	NR_173139.1		n.909C>T	non_coding_transcript_exon	Exon 5 of 5
LINC00632	NR_173141.1		n.652C>T	non_coding_transcript_exon	Exon 2 of 2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
LINC00632	ENST00000649329.2	MANE Select	n.1016C>T	non_coding_transcript_exon	Exon 5 of 5
LINC00632	ENST00000625883.2	TSL:6	n.652C>T	non_coding_transcript_exon	Exon 2 of 2
LINC00632	ENST00000648200.2		n.11758C>T	non_coding_transcript_exon	Exon 5 of 5

Frequencies

GnomAD3 genomes

AF:

0.0000897

AC:

AN:

111445

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000163

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000954

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000285

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000565

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000657

AC:

AN:

182561

AF XY:

0.0000298

show subpopulations

Gnomad AFR exome

AF:

0.000457

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000289

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000245

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000392

AC:

AN:

1097638

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

363056

show subpopulations

African (AFR)

AF:

0.000152

AC:

AN:

26377

American (AMR)

AF:

0.00

AC:

AN:

35123

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19343

East Asian (EAS)

AF:

0.000331

AC:

AN:

30200

South Asian (SAS)

AF:

0.00

AC:

AN:

53980

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40519

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4127

European-Non Finnish (NFE)

AF:

0.0000309

AC:

AN:

841896

Other (OTH)

AF:

0.0000651

AC:

AN:

46073

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome 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

GnomAD4 genome

AF:

0.0000897

AC:

AN:

111497

Hom.:

Cov.:

AF XY:

0.0000593

AC XY:

AN XY:

33755

show subpopulations

African (AFR)

AF:

0.000163

AC:

AN:

30689

American (AMR)

AF:

0.0000953

AC:

AN:

10498

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2644

East Asian (EAS)

AF:

0.000286

AC:

AN:

3492

South Asian (SAS)

AF:

0.00

AC:

AN:

2649

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6029

Middle Eastern (MID)

AF:

0.00

AC:

AN:

217

European-Non Finnish (NFE)

AF:

0.0000565

AC:

AN:

53068

Other (OTH)

AF:

0.00

AC:

AN:

1531

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

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:

0.0000712

Hom.:

Bravo

AF:

0.000132

ESP6500AA

AF:

0.000522

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000906

AC:

EpiCase

AF:

0.0000546

EpiControl

AF:

0.0000593

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

0.18

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.54

CADD

Benign

8.7

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.011

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.52

M_CAP

Benign

0.014

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PhyloP100

1.2

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.72

REVEL

Benign

0.087

Sift

Benign

0.75

Sift4G

Benign

0.30

Polyphen

1.0

Vest4

0.26

MutPred

0.45

Gain of MoRF binding (P = 0.0204)

MVP

0.92

MPC

0.97

ClinPred

0.14

GERP RS

3.7

Varity_R

0.056

gMVP

0.032

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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