ENST00000625883.2:n.917C>G

Variant names:

• chrX-140784004-C-G
• ENST00000649329.2:n.1281C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000625883.2(LINC00632):​n.917C>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 0.00000182 in 1,097,928 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.0000018 (0 hom. 1 hem.)
• Consequence: LINC00632 ENST00000625883.2 non_coding_transcript_exon
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.46
• Publications: 0 publications found

Genes affected

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

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

ACMG classification

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=0.05165142).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LINC00632	NR_173140.2	MANE Select	n.1281C>G		non_coding_transcript_exon	Exon 5 of 5
	LINC00632	NR_173139.1		n.1174C>G		non_coding_transcript_exon	Exon 5 of 5
	LINC00632	NR_173141.1		n.917C>G		non_coding_transcript_exon	Exon 2 of 2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LINC00632	ENST00000649329.2	MANE Select	n.1281C>G		non_coding_transcript_exon	Exon 5 of 5
	LINC00632	ENST00000625883.2	TSL:6	n.917C>G		non_coding_transcript_exon	Exon 2 of 2
	LINC00632	ENST00000648200.2		n.12023C>G		non_coding_transcript_exon	Exon 5 of 5

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome AF: 0.00000182 AC: 2 AN: 1097928 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 1 AN XY: 363326

African (AFR) AF: 0.00 AC: 0 AN: 26390

American (AMR) AF: 0.00 AC: 0 AN: 35181

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19357

East Asian (EAS) AF: 0.00 AC: 0 AN: 30202

South Asian (SAS) AF: 0.0000370 AC: 2 AN: 54089

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40519

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4133

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 841973

Other (OTH) AF: 0.00 AC: 0 AN: 46084

GnomAD4 genome Cov.: 24

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-1.1
CADD	Benign	1.5
DANN	Benign	0.80
DEOGEN2	Benign	0.017	T
FATHMM_MKL	Benign	0.052	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-1.5
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.038
Sift	Benign	0.47	T
Sift4G	Benign	0.41	T
Polyphen		0.48	P
Vest4		0.079
MutPred		0.33		Loss of ubiquitination at K121 (P = 0.0092)
MVP		0.43
MPC		0.30
ClinPred		0.075	T
GERP RS		-1.2
PromoterAI		0.015	Neutral
Varity_R		0.058
gMVP		0.019
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

hg19: chrX-139866169;