Genetic Variant ENST00000625883.2:n.955G>T (chrX-140784042-G-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 ENST00000625883.2(LINC00632):n.955G>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 0.000027 in 110,962 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 0 hem., cov: 24)

Exomes 𝑓: 0.0000027 ( 0 hom. 2 hem. )

Failed GnomAD Quality Control

Consequence

LINC00632
ENST00000625883.2 non_coding_transcript_exon

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -11.3

Publications

2 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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.020065427).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000625883.2. 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.1319G>T	non_coding_transcript_exon	Exon 5 of 5
LINC00632	NR_173139.1		n.1212G>T	non_coding_transcript_exon	Exon 5 of 5
LINC00632	NR_173141.1		n.955G>T	non_coding_transcript_exon	Exon 2 of 2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
LINC00632	ENST00000649329.2	MANE Select	n.1319G>T	non_coding_transcript_exon	Exon 5 of 5
LINC00632	ENST00000625883.2	TSL:6	n.955G>T	non_coding_transcript_exon	Exon 2 of 2
LINC00632	ENST00000648200.2		n.12061G>T	non_coding_transcript_exon	Exon 5 of 5

Frequencies

GnomAD3 genomes

AF:

0.0000270

AC:

AN:

110962

Hom.:

Cov.:

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:

0.0000567

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000109

AC:

AN:

182950

AF XY:

0.0000148

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000245

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000273

AC:

AN:

1098022

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

363406

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26388

American (AMR)

AF:

0.00

AC:

AN:

35205

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19371

East Asian (EAS)

AF:

0.00

AC:

AN:

30202

South Asian (SAS)

AF:

0.00

AC:

AN:

54126

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40516

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4134

European-Non Finnish (NFE)

AF:

0.00000356

AC:

AN:

841994

Other (OTH)

AF:

0.00

AC:

AN:

46086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000270

AC:

AN:

110962

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33292

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

30501

American (AMR)

AF:

0.00

AC:

AN:

10414

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2637

East Asian (EAS)

AF:

0.00

AC:

AN:

3496

South Asian (SAS)

AF:

0.00

AC:

AN:

2586

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5975

Middle Eastern (MID)

AF:

0.00

AC:

AN:

233

European-Non Finnish (NFE)

AF:

0.0000567

AC:

AN:

52931

Other (OTH)

AF:

0.00

AC:

AN:

1503

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000000000000888178), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.392

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:

0.00000756

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

0.060

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.0090

(source)

DANN

Benign

0.18

DEOGEN2

Benign

0.0033

FATHMM_MKL

Benign

0.0046

LIST_S2

Benign

0.17

M_CAP

Benign

0.0061

MetaRNN

Benign

0.020

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PhyloP100

-11

PrimateAI

Benign

0.19

PROVEAN

Benign

0.94

REVEL

Benign

0.0090

Sift

Benign

0.72

Sift4G

Benign

0.14

Polyphen

0.0

Vest4

0.066

MutPred

0.28

Loss of stability (P = 0.0439)

MVP

0.17

MPC

0.28

ClinPred

0.059

GERP RS

-8.4

PromoterAI

0.010

Neutral

(source)

Varity_R

0.031

gMVP

0.0067

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over