rs719988

Positions:

• chrX-85893361-G-A

Variant summary

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

The NM_000390.4(CHM):​c.1510+827C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 110,766 control chromosomes in the GnomAD database, including 3,333 homozygotes. There are 8,591 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 0.27 (3333 hom., 8591 hem., cov: 22)
• Consequence: CHM NM_000390.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0920

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHM	NM_000390.4	c.1510+827C>T		intron_variant		ENST00000357749.7	NP_000381.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHM	ENST00000357749.7	c.1510+827C>T		intron_variant		1	NM_000390.4	ENSP00000350386.2
CHM	ENST00000467744.2	n.127-30267C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.272 AC: 30169 AN: 110719 Hom.: 3334 Cov.: 22 AF XY: 0.260 AC XY: 8584 AN XY: 32991

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.250

Gnomad AMR AF: 0.383

Gnomad ASJ AF: 0.318

Gnomad EAS AF: 0.00421

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.313

Gnomad MID AF: 0.270

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.292

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

GnomAD4 genome AF: 0.272 AC: 30170 AN: 110766 Hom.: 3333 Cov.: 22 AF XY: 0.260 AC XY: 8591 AN XY: 33048

Gnomad4 AFR AF: 0.188

Gnomad4 AMR AF: 0.383

Gnomad4 ASJ AF: 0.318

Gnomad4 EAS AF: 0.00423

Gnomad4 SAS AF: 0.127

Gnomad4 FIN AF: 0.313

Gnomad4 NFE AF: 0.318

Gnomad4 OTH AF: 0.288

Alfa AF: 0.310 Hom.: 5266

Bravo AF: 0.279

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.7
DANN	Benign	0.34

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: rs719988; hg19: chrX-85148366;