rs1414341641

Variant names:

• chrX-154437141-C-T
• rs1414341641
• ENST00000630693.2:c.-114C>T

Variant summary

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

The ENST00000630693.2(GDI1):​c.-114C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000961 in 685,765 control chromosomes in the GnomAD database, including 2 homozygotes. There are 176 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 0.00085 (1 hom., 23 hem., cov: 22)
  • Exomes 𝑓: 0.00098 (1 hom. 153 hem.)
• Consequence: GDI1 ENST00000630693.2 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0510
• 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: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• non-syndromic X-linked intellectual disability

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant X-154437141-C-T is Benign according to our data. Variant chrX-154437141-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3024945.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000852 (94/110292) while in subpopulation NFE AF = 0.00155 (81/52240). AF 95% confidence interval is 0.00128. There are 1 homozygotes in GnomAd4. There are 23 alleles in the male GnomAd4 subpopulation. Median coverage is 22. This position passed quality control check.
• BS2: High Hemizygotes in GnomAd4 at 23 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000630693.2. 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
	GDI1	NM_001493.3	MANE Select	c.-114C>T		upstream_gene	N/A	NP_001484.1	A0A0S2Z3X8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GDI1	ENST00000630693.2	TSL:4	c.-114C>T		5_prime_UTR	Exon 1 of 5	ENSP00000486715.1	G5E9U5
	GDI1	ENST00000963418.1		c.-88-26C>T		intron	N/A	ENSP00000633477.1
	GDI1	ENST00000447750.7	TSL:1 MANE Select	c.-114C>T		upstream_gene	N/A	ENSP00000394071.2	P31150

Frequencies

GnomAD3 genomes AF: 0.000853 AC: 94 AN: 110251 Hom.: 1 Cov.: 22

Gnomad AFR AF: 0.000197

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000566

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000173

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00155

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000982 AC: 565 AN: 575473 Hom.: 1 Cov.: 9 AF XY: 0.00100 AC XY: 153 AN XY: 152261

African (AFR) AF: 0.0000763 AC: 1 AN: 13112

American (AMR) AF: 0.0000937 AC: 2 AN: 21341

Ashkenazi Jewish (ASJ) AF: 0.0000796 AC: 1 AN: 12555

East Asian (EAS) AF: 0.00 AC: 0 AN: 21846

South Asian (SAS) AF: 0.0000281 AC: 1 AN: 35558

European-Finnish (FIN) AF: 0.000893 AC: 31 AN: 34708

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2236

European-Non Finnish (NFE) AF: 0.00127 AC: 516 AN: 406367

Other (OTH) AF: 0.000468 AC: 13 AN: 27750

GnomAD4 genome AF: 0.000852 AC: 94 AN: 110292 Hom.: 1 Cov.: 22 AF XY: 0.000701 AC XY: 23 AN XY: 32790

African (AFR) AF: 0.000196 AC: 6 AN: 30556

American (AMR) AF: 0.000565 AC: 6 AN: 10620

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2631

East Asian (EAS) AF: 0.00 AC: 0 AN: 3419

South Asian (SAS) AF: 0.00 AC: 0 AN: 2661

European-Finnish (FIN) AF: 0.000173 AC: 1 AN: 5792

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 210

European-Non Finnish (NFE) AF: 0.00155 AC: 81 AN: 52240

Other (OTH) AF: 0.00 AC: 0 AN: 1506

Alfa AF: 0.00124 Hom.: 7

Bravo AF: 0.000759

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.6
DANN	Benign	0.86
PhyloP100		-0.051
PromoterAI		-0.031	Neutral
Mutation Taster		=300/0	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: rs1414341641; hg19: chrX-153665487;