rs4869931

Positions:

• chr6-150688753-A-G
• chr6-150688753-A-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLEKHG1	NM_001029884.3	c.-99+37967A>G		intron_variant		ENST00000696526.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLEKHG1	ENST00000696526.1	c.-99+37967A>G		intron_variant			NM_001029884.3	P1

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

Gnomad4 AFR AF: 0.520

Gnomad4 AMR AF: 0.288

Gnomad4 ASJ AF: 0.141

Gnomad4 EAS AF: 0.287

Gnomad4 SAS AF: 0.341

Gnomad4 FIN AF: 0.211

Gnomad4 NFE AF: 0.182

Gnomad4 OTH AF: 0.257

Alfa AF: 0.188 Hom.: 1307

Bravo AF: 0.307

Asia WGS AF: 0.373 AC: 1296 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.24
DANN	Benign	0.82

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

Publications

LitVar

Other links and lift over

dbSNP: rs4869931; hg19: chr6-151009889; COSMIC: COSV66235690;