chrX-140783988-T-C

Position:

• chrX-140783988-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The ENST00000648200.2(LINC00632):​n.12007T>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 0.00000455 in 1,097,878 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 Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.0000046 (0 hom. 1 hem.)
• Consequence: LINC00632 ENST00000648200.2 non_coding_transcript_exon
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -7.34

Genes affected

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

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

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.029226154).
• BP6: Variant X-140783988-T-C is Benign according to our data. Variant chrX-140783988-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2309179.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDR1	XR_006652813.2	n.9225A>G		non_coding_transcript_exon_variant	1/1
LINC00632	NR_173144.1	n.345-7014T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LINC00632	ENST00000648200.2	n.12007T>C		non_coding_transcript_exon_variant	5/5
CDR1	ENST00000674533.1	n.379A>G		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome AF: 0.00000455 AC: 5 AN: 1097878 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 1 AN XY: 363278

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: 0.00000594

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 24

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 26, 2022

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	0.065
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.0050
DANN	Benign	0.36
DEOGEN2	Benign	0.0035	T
FATHMM_MKL	Benign	0.0042	N
LIST_S2	Benign	0.27	T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.029	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.39	N
REVEL	Benign	0.0090
Sift	Benign	0.30	T
Sift4G	Benign	0.11	T
Polyphen		0.0	B
Vest4		0.068
MutPred		0.30		Loss of helix (P = 0.0558);
MVP		0.099
MPC		0.25
ClinPred		0.31	T
GERP RS		-7.5
Varity_R		0.047
gMVP		0.014

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-139866153;