rs4869931

Variant names:

• chr6-150688753-A-G
• rs4869931
• NM_001029884.3:c.-99+37967A>G

Your query was ambiguous. Multiple possible variants found:

• chr6-150688753-A-G
• chr6-150688753-A-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.-99+37967A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 152,132 control chromosomes in the GnomAD database, including 8,227 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 0.30 (8227 hom., cov: 33)
• Consequence: PLEKHG1 NM_001029884.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.945
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.514 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLEKHG1	NM_001029884.3	MANE Select	c.-99+37967A>G		intron	N/A	NP_001025055.1	Q9ULL1
	PLEKHG1	NM_001329798.2		c.79+4912A>G		intron	N/A	NP_001316727.1
	PLEKHG1	NM_001329799.2		c.23-44831A>G		intron	N/A	NP_001316728.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLEKHG1	ENST00000696526.1	MANE Select	c.-99+37967A>G		intron	N/A	ENSP00000512689.1	Q9ULL1
	PLEKHG1	ENST00000644968.1		c.-99+4871A>G		intron	N/A	ENSP00000496254.1	Q9ULL1
	PLEKHG1	ENST00000856903.1		c.-98-44831A>G		intron	N/A	ENSP00000526962.1

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44865 AN: 152014 Hom.: 8193 Cov.: 33

Gnomad AFR AF: 0.520

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.287

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.287

Gnomad SAS AF: 0.342

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.253

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

GnomAD4 genome AF: 0.295 AC: 44953 AN: 152132 Hom.: 8227 Cov.: 33 AF XY: 0.295 AC XY: 21935 AN XY: 74376

African (AFR) AF: 0.520 AC: 21566 AN: 41490

American (AMR) AF: 0.288 AC: 4395 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 488 AN: 3464

East Asian (EAS) AF: 0.287 AC: 1487 AN: 5180

South Asian (SAS) AF: 0.341 AC: 1645 AN: 4824

European-Finnish (FIN) AF: 0.211 AC: 2228 AN: 10582

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.182 AC: 12402 AN: 67996

Other (OTH) AF: 0.257 AC: 542 AN: 2112

Alfa AF: 0.208 Hom.: 2843

Bravo AF: 0.307

Asia WGS AF: 0.373 AC: 1296 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.24
DANN	Benign	0.82
PhyloP100		-0.94
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: rs4869931; hg19: chr6-151009889; COSMIC: COSV66235690;