6-150705265-T-C

Variant names:

• chr6-150705265-T-C
• rs6940976
• NM_001029884.3:c.-98-28319T>C

Variant summary

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

The NM_001029884.3(PLEKHG1):​c.-98-28319T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.757 in 152,230 control chromosomes in the GnomAD database, including 44,694 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 0.76 (44694 hom., cov: 34)
• Consequence: PLEKHG1 NM_001029884.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.845
• Publications: 1 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.848 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.-98-28319T>C		intron	N/A	NP_001025055.1
	PLEKHG1	NM_001329798.2		c.79+21424T>C		intron	N/A	NP_001316727.1
	PLEKHG1	NM_001329799.2		c.23-28319T>C		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.-98-28319T>C		intron	N/A	ENSP00000512689.1
	PLEKHG1	ENST00000644968.1		c.-99+21383T>C		intron	N/A	ENSP00000496254.1
	PLEKHG1	ENST00000644913.1		c.118+18275T>C		intron	N/A	ENSP00000493494.1

Frequencies

GnomAD3 genomes AF: 0.758 AC: 115237 AN: 152112 Hom.: 44682 Cov.: 34

Gnomad AFR AF: 0.587

Gnomad AMI AF: 0.887

Gnomad AMR AF: 0.693

Gnomad ASJ AF: 0.857

Gnomad EAS AF: 0.807

Gnomad SAS AF: 0.716

Gnomad FIN AF: 0.844

Gnomad MID AF: 0.816

Gnomad NFE AF: 0.854

Gnomad OTH AF: 0.782

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

GnomAD4 genome AF: 0.757 AC: 115274 AN: 152230 Hom.: 44694 Cov.: 34 AF XY: 0.755 AC XY: 56171 AN XY: 74430

African (AFR) AF: 0.587 AC: 24373 AN: 41514

American (AMR) AF: 0.691 AC: 10575 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.857 AC: 2976 AN: 3472

East Asian (EAS) AF: 0.807 AC: 4178 AN: 5174

South Asian (SAS) AF: 0.717 AC: 3459 AN: 4824

European-Finnish (FIN) AF: 0.844 AC: 8950 AN: 10606

Middle Eastern (MID) AF: 0.813 AC: 239 AN: 294

European-Non Finnish (NFE) AF: 0.854 AC: 58061 AN: 68024

Other (OTH) AF: 0.782 AC: 1654 AN: 2116

Alfa AF: 0.817 Hom.: 64127

Bravo AF: 0.740

Asia WGS AF: 0.718 AC: 2501 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	9.0
DANN	Benign	0.69
PhyloP100		0.84
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: rs6940976; hg19: chr6-151026401;