X-86033051-A-G

Position:

• chrX-86033051-A-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000390.4(CHM):​c.50-5494T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.82 (26330 hom., 26417 hem., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: CHM NM_000390.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.259

Genes affected

CHM (HGNC:1940): (CHM Rab escort protein) This gene encodes component A of the RAB geranylgeranyl transferase holoenzyme. In the dimeric holoenzyme, this subunit binds unprenylated Rab GTPases and then presents them to the catalytic Rab GGTase subunit for the geranylgeranyl transfer reaction. Rab GTPases need to be geranylgeranyled on either one or two cysteine residues in their C-terminus to localize to the correct intracellular membrane. Mutations in this gene are a cause of choroideremia; also known as tapetochoroidal dystrophy (TCD). This X-linked disease is characterized by progressive dystrophy of the choroid, retinal pigment epithelium and retina. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Mar 2016]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHM	NM_000390.4	c.50-5494T>C		intron_variant		ENST00000357749.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHM	ENST00000357749.7	c.50-5494T>C		intron_variant		1	NM_000390.4	P1
CHM	ENST00000615443.1	c.50-5494T>C		intron_variant		1
CHM	ENST00000467744.2	n.60-5494T>C		intron_variant, non_coding_transcript_variant		5
CHM	ENST00000483950.1	n.79-5494T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.817 AC: 89885 AN: 110035 Hom.: 26330 Cov.: 23 AF XY: 0.817 AC XY: 26359 AN XY: 32253

Gnomad AFR AF: 0.962

Gnomad AMI AF: 0.612

Gnomad AMR AF: 0.824

Gnomad ASJ AF: 0.734

Gnomad EAS AF: 0.889

Gnomad SAS AF: 0.905

Gnomad FIN AF: 0.770

Gnomad MID AF: 0.735

Gnomad NFE AF: 0.736

Gnomad OTH AF: 0.790

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.817 AC: 89940 AN: 110084 Hom.: 26330 Cov.: 23 AF XY: 0.818 AC XY: 26417 AN XY: 32312

Gnomad4 AFR AF: 0.962

Gnomad4 AMR AF: 0.824

Gnomad4 ASJ AF: 0.734

Gnomad4 EAS AF: 0.889

Gnomad4 SAS AF: 0.906

Gnomad4 FIN AF: 0.770

Gnomad4 NFE AF: 0.736

Gnomad4 OTH AF: 0.788

Alfa AF: 0.770 Hom.: 20942

Bravo AF: 0.827

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.5
DANN	Benign	0.65

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

Other links and lift over

dbSNP: rs2038193; hg19: chrX-85288055;