Genetic Variant LINC00632:n.652C>T (chrX-140783739-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -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

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 made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

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

BS2

High Hemizygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
LINC00632	NR_173139.1 link	n.909C>T	non_coding_transcript_exon_variant	Exon 5 of 5
LINC00632	NR_173140.2 link	n.1016C>T	non_coding_transcript_exon_variant	Exon 5 of 5
LINC00632	NR_173141.1 link	n.652C>T	non_coding_transcript_exon_variant	Exon 2 of 2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
LINC00632	ENST00000625883.2 link	n.652C>T	non_coding_transcript_exon_variant	Exon 2 of 2	6
LINC00632	ENST00000648200.2 link	n.11758C>T	non_coding_transcript_exon_variant	Exon 5 of 5
LINC00632	ENST00000648347.1 link	n.448C>T	non_coding_transcript_exon_variant	Exon 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.0000897

AC:

AN:

111445

Hom.:

Cov.:

AF XY:

0.0000594

AC XY:

AN XY:

33693

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

GnomAD3 exomes

AF:

0.0000657

AC:

AN:

182561

Hom.:

AF XY:

0.0000298

AC XY:

AN XY:

67099

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 SAS exome

AF:

0.00

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

Gnomad4 AFR exome

AF:

0.000152

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000331

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000309

Gnomad4 OTH exome

AF:

0.0000651

GnomAD4 genome

AF:

0.0000897

AC:

AN:

111497

Hom.:

Cov.:

AF XY:

0.0000593

AC XY:

AN XY:

33755

show subpopulations

Gnomad4 AFR

AF:

0.000163

Gnomad4 AMR

AF:

0.0000953

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000286

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000565

Gnomad4 OTH

AF:

0.00

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

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 22, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.628G>A (p.G210R) alteration is located in exon 1 (coding exon 1) of the CDR1 gene. This alteration results from a G to A substitution at nucleotide position 628, causing the glycine (G) at amino acid position 210 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.54

CADD

Benign

8.7

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

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over