6-150804115-G-T

Variant names:

• chr6-150804115-G-T
• rs10046456
• NM_001029884.3:c.781-495G>T

Variant summary

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

The NM_001029884.3(PLEKHG1):​c.781-495G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.10 (973 hom., cov: 20)
• Consequence: PLEKHG1 NM_001029884.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.303
• Publications: 3 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.221 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.781-495G>T		intron	N/A	NP_001025055.1
	PLEKHG1	NM_001329798.2		c.958-495G>T		intron	N/A	NP_001316727.1
	PLEKHG1	NM_001329799.2		c.901-495G>T		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.781-495G>T		intron	N/A	ENSP00000512689.1
	PLEKHG1	ENST00000475490.1	TSL:1	n.322-495G>T		intron	N/A	ENSP00000433107.1
	PLEKHG1	ENST00000358517.6	TSL:5	c.781-495G>T		intron	N/A	ENSP00000351318.2

Frequencies

GnomAD3 genomes AF: 0.100 AC: 12357 AN: 123392 Hom.: 976 Cov.: 20

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.00118

Gnomad AMR AF: 0.0524

Gnomad ASJ AF: 0.0750

Gnomad EAS AF: 0.234

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.0333

Gnomad NFE AF: 0.0561

Gnomad OTH AF: 0.0919

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

GnomAD4 genome AF: 0.100 AC: 12344 AN: 123420 Hom.: 973 Cov.: 20 AF XY: 0.104 AC XY: 6054 AN XY: 57978

African (AFR) AF: 0.189 AC: 5962 AN: 31500

American (AMR) AF: 0.0523 AC: 586 AN: 11202

Ashkenazi Jewish (ASJ) AF: 0.0750 AC: 243 AN: 3238

East Asian (EAS) AF: 0.233 AC: 953 AN: 4092

South Asian (SAS) AF: 0.103 AC: 384 AN: 3728

European-Finnish (FIN) AF: 0.117 AC: 569 AN: 4858

Middle Eastern (MID) AF: 0.0253 AC: 5 AN: 198

European-Non Finnish (NFE) AF: 0.0562 AC: 3489 AN: 62132

Other (OTH) AF: 0.0937 AC: 152 AN: 1622

Alfa AF: 0.0690 Hom.: 1475

Asia WGS AF: 0.148 AC: 510 AN: 3452

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.96
DANN	Benign	0.27
PhyloP100		-0.30
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: rs10046456; hg19: chr6-151125251;