rs17080102

Positions:

• chr6-150683634-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001029884.3(PLEKHG1):​c.-99+32848G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0887 in 401,208 control chromosomes in the GnomAD database, including 1,938 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 0.087 (650 hom., cov: 31)
  • Exomes 𝑓: 0.090 (1288 hom.)
• Consequence: PLEKHG1 NM_001029884.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.579

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.15 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLEKHG1	NM_001029884.3	c.-99+32848G>C		intron_variant		ENST00000696526.1	NP_001025055.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLEKHG1	ENST00000696526.1	c.-99+32848G>C		intron_variant			NM_001029884.3	ENSP00000512689.1
PLEKHG1	ENST00000644968	c.-347G>C		5_prime_UTR_variant	1/16			ENSP00000496254.1
PLEKHG1	ENST00000367326.1	c.-99+32848G>C		intron_variant		3		ENSP00000356295.1
PLEKHG1	ENST00000644996.1	n.467+32848G>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.0865 AC: 13142 AN: 151998 Hom.: 641 Cov.: 31

Gnomad AFR AF: 0.0997

Gnomad AMI AF: 0.0978

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.0473

Gnomad EAS AF: 0.0655

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.0801

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0661

Gnomad OTH AF: 0.0885

GnomAD4 exome AF: 0.0900 AC: 22429 AN: 249092 Hom.: 1288 Cov.: 4 AF XY: 0.0976 AC XY: 13100 AN XY: 134290

Gnomad4 AFR exome AF: 0.107

Gnomad4 AMR exome AF: 0.160

Gnomad4 ASJ exome AF: 0.0487

Gnomad4 EAS exome AF: 0.0708

Gnomad4 SAS exome AF: 0.164

Gnomad4 FIN exome AF: 0.0751

Gnomad4 NFE exome AF: 0.0679

Gnomad4 OTH exome AF: 0.0835

GnomAD4 genome AF: 0.0865 AC: 13163 AN: 152116 Hom.: 650 Cov.: 31 AF XY: 0.0886 AC XY: 6589 AN XY: 74358

Gnomad4 AFR AF: 0.0996

Gnomad4 AMR AF: 0.138

Gnomad4 ASJ AF: 0.0473

Gnomad4 EAS AF: 0.0651

Gnomad4 SAS AF: 0.160

Gnomad4 FIN AF: 0.0801

Gnomad4 NFE AF: 0.0661

Gnomad4 OTH AF: 0.0876

Alfa AF: 0.0764 Hom.: 60

Bravo AF: 0.0896

Asia WGS AF: 0.123 AC: 427 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.2
DANN	Benign	0.71

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: rs17080102; hg19: chr6-151004770;