rs185552165

Variant names:

• chrX-154438512-C-A
• rs185552165
• NM_001493.3:c.46-11C>A

Your query was ambiguous. Multiple possible variants found:

• chrX-154438512-C-A
• chrX-154438512-C-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001493.3(GDI1):​c.46-11C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000424 in 1,119,127 control chromosomes in the GnomAD database, including 1 homozygotes. There are 132 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0018 (0 hom., 52 hem., cov: 23)
  • Exomes 𝑓: 0.00027 (1 hom. 80 hem.)
• Consequence: GDI1 NM_001493.3 intron
• Scores: Splicing: ADA: 0.0002234
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.551
• Publications: 0 publications found

Genes affected

GDI1 (HGNC:4226): (GDP dissociation inhibitor 1) GDP dissociation inhibitors are proteins that regulate the GDP-GTP exchange reaction of members of the rab family, small GTP-binding proteins of the ras superfamily, that are involved in vesicular trafficking of molecules between cellular organelles. GDIs slow the rate of dissociation of GDP from rab proteins and release GDP from membrane-bound rabs. GDI1 is expressed primarily in neural and sensory tissues. Mutations in GDI1 have been linked to X-linked nonspecific cognitive disability. [provided by RefSeq, Jul 2008]

GDI1 Gene-Disease associations (from GenCC):

• intellectual disability, X-linked 41

  Inheritance: XL Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• non-syndromic X-linked intellectual disability

  Inheritance: XL Classification: MODERATE, SUPPORTIVE Submitted by: ClinGen, Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant X-154438512-C-A is Benign according to our data. Variant chrX-154438512-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 376795.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00179 (200/112001) while in subpopulation AFR AF = 0.00623 (192/30841). AF 95% confidence interval is 0.0055. There are 0 homozygotes in GnomAd4. There are 52 alleles in the male GnomAd4 subpopulation. Median coverage is 23. This position passed quality control check.
• BS2: High Hemizygotes in GnomAd4 at 52 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GDI1	NM_001493.3	c.46-11C>A		intron_variant	Intron 1 of 10	ENST00000447750.7	NP_001484.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GDI1	ENST00000447750.7	c.46-11C>A		intron_variant	Intron 1 of 10	1	NM_001493.3	ENSP00000394071.2

Frequencies

GnomAD3 genomes AF: 0.00178 AC: 199 AN: 111949 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00621

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000376

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: 0.0000189

Gnomad OTH AF: 0.00200

GnomAD2 exomes AF: 0.000575 AC: 105 AN: 182738 AF XY: 0.000267

Gnomad AFR exome AF: 0.00696

Gnomad AMR exome AF: 0.000183

Gnomad ASJ exome AF: 0.000134

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000859

Gnomad OTH exome AF: 0.000222

GnomAD4 exome AF: 0.000272 AC: 274 AN: 1007126 Hom.: 1 Cov.: 22 AF XY: 0.000264 AC XY: 80 AN XY: 302544

African (AFR) AF: 0.00834 AC: 206 AN: 24703

American (AMR) AF: 0.000142 AC: 5 AN: 35108

Ashkenazi Jewish (ASJ) AF: 0.000212 AC: 4 AN: 18839

East Asian (EAS) AF: 0.00 AC: 0 AN: 29836

South Asian (SAS) AF: 0.0000192 AC: 1 AN: 52155

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40264

Middle Eastern (MID) AF: 0.00102 AC: 4 AN: 3926

European-Non Finnish (NFE) AF: 0.0000395 AC: 30 AN: 759253

Other (OTH) AF: 0.000558 AC: 24 AN: 43042

GnomAD4 genome AF: 0.00179 AC: 200 AN: 112001 Hom.: 0 Cov.: 23 AF XY: 0.00152 AC XY: 52 AN XY: 34183

African (AFR) AF: 0.00623 AC: 192 AN: 30841

American (AMR) AF: 0.000375 AC: 4 AN: 10662

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 3547

South Asian (SAS) AF: 0.00 AC: 0 AN: 2698

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6155

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 218

European-Non Finnish (NFE) AF: 0.0000189 AC: 1 AN: 53022

Other (OTH) AF: 0.00197 AC: 3 AN: 1522

Alfa AF: 0.00130 Hom.: 6

Bravo AF: 0.00233

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jan 02, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.6
DANN	Benign	0.72
PhyloP100		-0.55
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00022
dbscSNV1_RF	Benign	0.060
SpliceAI score (max)		0.090		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: rs185552165; hg19: chrX-153666858;