rs75253868

Variant names:

• chr6-150781694-T-A
• rs75253868
• NM_001029884.3:c.513-4696T>A

Your query was ambiguous. Multiple possible variants found:

• chr6-150781694-T-A
• chr6-150781694-T-C
• chr6-150781694-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001029884.3(PLEKHG1):​c.513-4696T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0498 in 152,184 control chromosomes in the GnomAD database, including 385 homozygotes. 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 0.050 (385 hom., cov: 30)
• Consequence: PLEKHG1 NM_001029884.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.915
• Publications: 7 publications found

Genes affected

PLEKHG1 (HGNC:20884): (pleckstrin homology and RhoGEF domain containing G1) Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in regulation of small GTPase mediated signal transduction. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

PLEKHG1 Gene-Disease associations (from GenCC):

• periventricular leukomalacia

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001029884.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLEKHG1	NM_001029884.3	MANE Select	c.513-4696T>A		intron	N/A	NP_001025055.1
	PLEKHG1	NM_001329798.2		c.690-4696T>A		intron	N/A	NP_001316727.1
	PLEKHG1	NM_001329799.2		c.633-4696T>A		intron	N/A	NP_001316728.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLEKHG1	ENST00000696526.1	MANE Select	c.513-4696T>A		intron	N/A	ENSP00000512689.1
	PLEKHG1	ENST00000475490.1	TSL:1	n.54-4696T>A		intron	N/A	ENSP00000433107.1
	PLEKHG1	ENST00000358517.6	TSL:5	c.513-4696T>A		intron	N/A	ENSP00000351318.2

Frequencies

GnomAD3 genomes AF: 0.0498 AC: 7574 AN: 152068 Hom.: 379 Cov.: 30

Gnomad AFR AF: 0.0224

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.0423

Gnomad EAS AF: 0.232

Gnomad SAS AF: 0.0778

Gnomad FIN AF: 0.0817

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0327

Gnomad OTH AF: 0.0589

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

GnomAD4 genome AF: 0.0498 AC: 7583 AN: 152184 Hom.: 385 Cov.: 30 AF XY: 0.0547 AC XY: 4069 AN XY: 74400

African (AFR) AF: 0.0223 AC: 926 AN: 41566

American (AMR) AF: 0.113 AC: 1729 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0423 AC: 147 AN: 3472

East Asian (EAS) AF: 0.231 AC: 1189 AN: 5146

South Asian (SAS) AF: 0.0766 AC: 369 AN: 4816

European-Finnish (FIN) AF: 0.0817 AC: 863 AN: 10564

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0327 AC: 2223 AN: 68012

Other (OTH) AF: 0.0620 AC: 131 AN: 2112

Alfa AF: 0.0139 Hom.: 4

Bravo AF: 0.0505

Asia WGS AF: 0.151 AC: 524 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.0
DANN	Benign	0.68
PhyloP100		0.92
Mutation Taster		=100/0	polymorphism (auto)

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: rs75253868; hg19: chr6-151102830;