rs747278560

Variant names:

• chrX-85864663-T-G
• rs747278560
• NM_000390.4:c.1929A>C

Your query was ambiguous. Multiple possible variants found:

• chrX-85864663-T-G
• chrX-85864663-T-C

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_000390.4(CHM):​c.1929A>C​(p.Thr643Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000108 in 1,208,528 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 43 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000090 (0 hom., 0 hem., cov: 23)
  • Exomes 𝑓: 0.00012 (0 hom. 43 hem.)
• Consequence: CHM NM_000390.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 1.81
• 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: G2P, Orphanet, Illumina, Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant X-85864663-T-G is Benign according to our data. Variant chrX-85864663-T-G is described in ClinVar as Benign. ClinVar VariationId is 1165534.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.81 with no splicing effect.
• BS2: High Hemizygotes in GnomAdExome4 at 43 XL gene

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.1929A>C	p.Thr643Thr	synonymous	Exon 15 of 15	NP_000381.1	P24386-1
	CHM	NM_001320959.1		c.1485A>C	p.Thr495Thr	synonymous	Exon 15 of 15	NP_001307888.1	B4DRL9
	CHM	NM_001362517.1		c.1485A>C	p.Thr495Thr	synonymous	Exon 15 of 15	NP_001349446.1	B4DRL9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHM	ENST00000357749.7	TSL:1 MANE Select	c.1929A>C	p.Thr643Thr	synonymous	Exon 15 of 15	ENSP00000350386.2	P24386-1
	CHM	ENST00000891168.1		c.1926A>C	p.Thr642Thr	synonymous	Exon 15 of 15	ENSP00000561227.1
	CHM	ENST00000891170.1		c.1914A>C	p.Thr638Thr	synonymous	Exon 15 of 15	ENSP00000561229.1

Frequencies

GnomAD3 genomes AF: 0.00000895 AC: 1 AN: 111678 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000188

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000167 AC: 3 AN: 179657 AF XY: 0.0000310

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000251

Gnomad OTH exome AF: 0.000226

GnomAD4 exome AF: 0.000118 AC: 129 AN: 1096850 Hom.: 0 Cov.: 29 AF XY: 0.000119 AC XY: 43 AN XY: 362384

African (AFR) AF: 0.00 AC: 0 AN: 26389

American (AMR) AF: 0.00 AC: 0 AN: 35143

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19365

East Asian (EAS) AF: 0.00 AC: 0 AN: 30119

South Asian (SAS) AF: 0.0000557 AC: 3 AN: 53850

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40440

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4109

European-Non Finnish (NFE) AF: 0.000149 AC: 125 AN: 841401

Other (OTH) AF: 0.0000217 AC: 1 AN: 46034

GnomAD4 genome AF: 0.00000895 AC: 1 AN: 111678 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 33842

African (AFR) AF: 0.00 AC: 0 AN: 30690

American (AMR) AF: 0.00 AC: 0 AN: 10491

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2650

East Asian (EAS) AF: 0.00 AC: 0 AN: 3534

South Asian (SAS) AF: 0.00 AC: 0 AN: 2663

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6034

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 237

European-Non Finnish (NFE) AF: 0.0000188 AC: 1 AN: 53199

Other (OTH) AF: 0.00 AC: 0 AN: 1499

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Choroideremia (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.7
DANN	Benign	0.69
PhyloP100		1.8
Mutation Taster		=100/0	polymorphism

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: rs747278560; hg19: chrX-85119668;