chrX-85932135-G-T

Position:

• chrX-85932135-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000357749.7(CHM):​c.1167-20797C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 111,205 control chromosomes in the GnomAD database, including 2,034 homozygotes. There are 6,932 hemizygotes in GnomAD. 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 0.21 (2034 hom., 6932 hem., cov: 23)
• Consequence: CHM ENST00000357749.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.881

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.506 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHM	NM_000390.4	c.1167-20797C>A		intron_variant		ENST00000357749.7	NP_000381.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHM	ENST00000357749.7	c.1167-20797C>A		intron_variant		1	NM_000390.4	ENSP00000350386	P1
CHM	ENST00000467744.2	n.127-69041C>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.207 AC: 23060 AN: 111156 Hom.: 2035 Cov.: 23 AF XY: 0.208 AC XY: 6932 AN XY: 33372

Gnomad AFR AF: 0.0907

Gnomad AMI AF: 0.176

Gnomad AMR AF: 0.239

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.527

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.251

Gnomad MID AF: 0.296

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.197

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

GnomAD4 genome AF: 0.207 AC: 23053 AN: 111205 Hom.: 2034 Cov.: 23 AF XY: 0.207 AC XY: 6932 AN XY: 33431

Gnomad4 AFR AF: 0.0905

Gnomad4 AMR AF: 0.239

Gnomad4 ASJ AF: 0.211

Gnomad4 EAS AF: 0.526

Gnomad4 SAS AF: 0.351

Gnomad4 FIN AF: 0.251

Gnomad4 NFE AF: 0.236

Gnomad4 OTH AF: 0.197

Alfa AF: 0.237 Hom.: 10328

Bravo AF: 0.205

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.81
DANN	Benign	0.55

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: rs11092732; hg19: chrX-85187140;