X-86033051-A-G

Variant names:

• chrX-86033051-A-G
• rs2038193
• NM_000390.4:c.50-5494T>C

Variant summary

Our verdict is Likely benign. The variant received -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
• Publications: 0 publications found

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]

CHM Gene-Disease associations (from GenCC):

• choroideremia

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P, ClinGen, Illumina

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000390.4. 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
	CHM	NM_000390.4	MANE Select	c.50-5494T>C		intron	N/A	NP_000381.1
	CHM	NM_001320959.1		c.-395-5494T>C		intron	N/A	NP_001307888.1
	CHM	NM_001362517.1		c.-395-5494T>C		intron	N/A	NP_001349446.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHM	ENST00000357749.7	TSL:1 MANE Select	c.50-5494T>C		intron	N/A	ENSP00000350386.2
	CHM	ENST00000615443.1	TSL:1	c.50-5494T>C		intron	N/A	ENSP00000484306.1
	CHM	ENST00000891168.1		c.50-5494T>C		intron	N/A	ENSP00000561227.1

Frequencies

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

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

African (AFR) AF: 0.962 AC: 29256 AN: 30400

American (AMR) AF: 0.824 AC: 8460 AN: 10266

Ashkenazi Jewish (ASJ) AF: 0.734 AC: 1931 AN: 2631

East Asian (EAS) AF: 0.889 AC: 3102 AN: 3490

South Asian (SAS) AF: 0.906 AC: 2336 AN: 2577

European-Finnish (FIN) AF: 0.770 AC: 4401 AN: 5718

Middle Eastern (MID) AF: 0.742 AC: 158 AN: 213

European-Non Finnish (NFE) AF: 0.736 AC: 38693 AN: 52606

Other (OTH) AF: 0.788 AC: 1193 AN: 1513

Alfa AF: 0.781 Hom.: 32395

Bravo AF: 0.827

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.5
DANN	Benign	0.65
PhyloP100		0.26
Mutation Taster		=100/0	polymorphism (auto)

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

dbSNP: rs2038193; hg19: chrX-85288055;