rs75253868

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLEKHG1	NM_001029884.3	c.513-4696T>A		intron_variant		ENST00000696526.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLEKHG1	ENST00000696526.1	c.513-4696T>A		intron_variant			NM_001029884.3	P1
PLEKHG1	ENST00000475490.1	c.54-4696T>A		intron_variant, NMD_transcript_variant		1
PLEKHG1	ENST00000358517.6	c.513-4696T>A		intron_variant		5		P1
PLEKHG1	ENST00000644968.1	c.513-4696T>A		intron_variant				P1

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

Gnomad4 AFR AF: 0.0223

Gnomad4 AMR AF: 0.113

Gnomad4 ASJ AF: 0.0423

Gnomad4 EAS AF: 0.231

Gnomad4 SAS AF: 0.0766

Gnomad4 FIN AF: 0.0817

Gnomad4 NFE AF: 0.0327

Gnomad4 OTH AF: 0.0620

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.0
DANN	Benign	0.68

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: rs75253868; hg19: chr6-151102830;