Genetic Variant LINC00632:n.556T>C (chrX-140783643-T-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NR_173139.1(LINC00632):n.813T>C 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 0.0000198 in 1,209,729 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 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 0.0000089 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.000021 ( 0 hom. 6 hem. )

Consequence

LINC00632
NR_173139.1 non_coding_transcript_exon

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.00300

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06528041).

BS2

High Hemizygotes in GnomAdExome4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
LINC00632	NR_173139.1 link	n.813T>C	non_coding_transcript_exon_variant	Exon 5 of 5
LINC00632	NR_173140.2 link	n.920T>C	non_coding_transcript_exon_variant	Exon 5 of 5
LINC00632	NR_173141.1 link	n.556T>C	non_coding_transcript_exon_variant	Exon 2 of 2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
LINC00632	ENST00000625883.2 link	n.556T>C	non_coding_transcript_exon_variant	Exon 2 of 2	6
LINC00632	ENST00000648200.2 link	n.11662T>C	non_coding_transcript_exon_variant	Exon 5 of 5
LINC00632	ENST00000648347.1 link	n.352T>C	non_coding_transcript_exon_variant	Exon 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.00000892

AC:

AN:

112097

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34271

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000275

AC:

AN:

182055

Hom.:

AF XY:

0.0000300

AC XY:

AN XY:

66621

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000614

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000210

AC:

AN:

1097632

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

363056

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000273

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000892

AC:

AN:

112097

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34271

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000188

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.0000546

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 01, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.724A>G (p.K242E) alteration is located in exon 1 (coding exon 1) of the CDR1 gene. This alteration results from a A to G substitution at nucleotide position 724, causing the lysine (K) at amino acid position 242 to be replaced by a glutamic acid (E). 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

Uncertain

0.41

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.010

FATHMM_MKL

Benign

0.028

LIST_S2

Benign

0.42

M_CAP

Benign

0.035

MetaRNN

Benign

0.065

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.14

REVEL

Benign

0.0030

Sift

Benign

0.62

Sift4G

Pathogenic

0.0

Polyphen

0.22

Vest4

0.23

MutPred

0.31

Loss of ubiquitination at K242 (P = 0.0141);

MVP

0.54

MPC

0.65

ClinPred

0.068

GERP RS

1.4

Varity_R

0.13

gMVP

0.035

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

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