Genetic Variant LINC00632:n.709A>G (chrX-140783796-A-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NR_173139.1(LINC00632):n.966A>G 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 0.000121 in 1,207,503 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 53 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., 4 hem., cov: 24)

Exomes 𝑓: 0.00012 ( 0 hom. 49 hem. )

Consequence

LINC00632
NR_173139.1 non_coding_transcript_exon

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.82

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03625685).

BP6

Variant X-140783796-A-G is Benign according to our data. Variant chrX-140783796-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3489720.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
LINC00632	NR_173139.1 link	n.966A>G	non_coding_transcript_exon_variant	Exon 5 of 5
LINC00632	NR_173140.2 link	n.1073A>G	non_coding_transcript_exon_variant	Exon 5 of 5
LINC00632	NR_173141.1 link	n.709A>G	non_coding_transcript_exon_variant	Exon 2 of 2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
LINC00632	ENST00000625883.2 link	n.709A>G	non_coding_transcript_exon_variant	Exon 2 of 2	6
LINC00632	ENST00000648200.2 link	n.11815A>G	non_coding_transcript_exon_variant	Exon 5 of 5
LINC00632	ENST00000648347.1 link	n.505A>G	non_coding_transcript_exon_variant	Exon 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

111973

Hom.:

Cov.:

AF XY:

0.000117

AC XY:

AN XY:

34277

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000946

Gnomad ASJ

AF:

0.000756

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000169

Gnomad OTH

AF:

0.00133

GnomAD3 exomes

AF:

0.000172

AC:

AN:

180475

Hom.:

AF XY:

0.000215

AC XY:

AN XY:

65153

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000222

Gnomad ASJ exome

AF:

0.000417

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000385

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000161

Gnomad OTH exome

AF:

0.000453

GnomAD4 exome

AF:

0.000120

AC:

132

AN:

1095478

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

361934

show subpopulations

Gnomad4 AFR exome

AF:

0.0000380

Gnomad4 AMR exome

AF:

0.000172

Gnomad4 ASJ exome

AF:

0.000831

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000280

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000738

Gnomad4 OTH exome

AF:

0.000348

GnomAD4 genome

AF:

0.000125

AC:

AN:

112025

Hom.:

Cov.:

AF XY:

0.000116

AC XY:

AN XY:

34339

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000945

Gnomad4 ASJ

AF:

0.000756

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000169

Gnomad4 OTH

AF:

0.00131

Alfa

AF:

0.000131

Hom.:

Bravo

AF:

0.000125

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000297

AC:

ExAC

AF:

0.000148

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Nov 13, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.66

CADD

Benign

0.37

DANN

Benign

0.21

DEOGEN2

Benign

0.033

FATHMM_MKL

Benign

0.030

LIST_S2

Benign

0.21

M_CAP

Benign

0.011

MetaRNN

Benign

0.036

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

PrimateAI

Benign

0.24

PROVEAN

Benign

-1.4

REVEL

Benign

0.049

Sift

Benign

0.20

Sift4G

Pathogenic

0.0

Polyphen

0.0010

Vest4

0.11

MutPred

0.69

Gain of sheet (P = 0.0221);

MVP

0.37

MPC

0.44

ClinPred

0.10

GERP RS

-1.1

Varity_R

0.13

gMVP

0.027

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