rs17080102

Variant names:

• chr6-150683634-G-C
• rs17080102
• NM_001029884.3:c.-99+32848G>C

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+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
• Publications: 27 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=-0.83).
• 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 rank	MANE	Protein	UniProt
PLEKHG1	NM_001029884.3	c.-99+32848G>C		intron_variant	Intron 2 of 16	ENST00000696526.1	NP_001025055.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLEKHG1	ENST00000696526.1	c.-99+32848G>C		intron_variant	Intron 2 of 16		NM_001029884.3	ENSP00000512689.1
PLEKHG1	ENST00000644968.1	c.-347G>C		5_prime_UTR_variant	Exon 1 of 16			ENSP00000496254.1
PLEKHG1	ENST00000367326.1	c.-99+32848G>C		intron_variant	Intron 3 of 3	3		ENSP00000356295.1
PLEKHG1	ENST00000644996.1	n.467+32848G>C		intron_variant	Intron 3 of 3

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

African (AFR) AF: 0.107 AC: 653 AN: 6116

American (AMR) AF: 0.160 AC: 1629 AN: 10204

Ashkenazi Jewish (ASJ) AF: 0.0487 AC: 230 AN: 4724

East Asian (EAS) AF: 0.0708 AC: 531 AN: 7496

South Asian (SAS) AF: 0.164 AC: 6936 AN: 42252

European-Finnish (FIN) AF: 0.0751 AC: 650 AN: 8660

Middle Eastern (MID) AF: 0.112 AC: 266 AN: 2366

European-Non Finnish (NFE) AF: 0.0679 AC: 10599 AN: 156072

Other (OTH) AF: 0.0835 AC: 935 AN: 11202

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

African (AFR) AF: 0.0996 AC: 4133 AN: 41478

American (AMR) AF: 0.138 AC: 2105 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0473 AC: 164 AN: 3468

East Asian (EAS) AF: 0.0651 AC: 336 AN: 5164

South Asian (SAS) AF: 0.160 AC: 769 AN: 4812

European-Finnish (FIN) AF: 0.0801 AC: 848 AN: 10590

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.0661 AC: 4497 AN: 68010

Other (OTH) AF: 0.0876 AC: 185 AN: 2112

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
PhyloP100		0.58
PromoterAI		0.051	Neutral
Mutation Taster		=97/3	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: rs17080102; hg19: chr6-151004770;