chr6-150775283-C-T

Variant names:

• chr6-150775283-C-T
• rs742636
• NM_001029884.3:c.512+6545C>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.512+6545C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0729 in 152,168 control chromosomes in the GnomAD database, including 462 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 0.073 (462 hom., cov: 32)
• Consequence: PLEKHG1 NM_001029884.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.174
• Publications: 3 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0833 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLEKHG1	NM_001029884.3	c.512+6545C>T		intron_variant	Intron 4 of 16	ENST00000696526.1	NP_001025055.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLEKHG1	ENST00000696526.1	c.512+6545C>T		intron_variant	Intron 4 of 16		NM_001029884.3	ENSP00000512689.1
PLEKHG1	ENST00000475490.1	n.53+6545C>T		intron_variant	Intron 1 of 14	1		ENSP00000433107.1
PLEKHG1	ENST00000358517.6	c.512+6545C>T		intron_variant	Intron 3 of 15	5		ENSP00000351318.2
PLEKHG1	ENST00000644968.1	c.512+6545C>T		intron_variant	Intron 3 of 15			ENSP00000496254.1

Frequencies

GnomAD3 genomes AF: 0.0729 AC: 11085 AN: 152050 Hom.: 463 Cov.: 32

Gnomad AFR AF: 0.0789

Gnomad AMI AF: 0.0758

Gnomad AMR AF: 0.0874

Gnomad ASJ AF: 0.0717

Gnomad EAS AF: 0.0464

Gnomad SAS AF: 0.0782

Gnomad FIN AF: 0.0241

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.0741

Gnomad OTH AF: 0.0958

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

GnomAD4 genome AF: 0.0729 AC: 11087 AN: 152168 Hom.: 462 Cov.: 32 AF XY: 0.0715 AC XY: 5319 AN XY: 74398

African (AFR) AF: 0.0788 AC: 3273 AN: 41514

American (AMR) AF: 0.0872 AC: 1333 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0717 AC: 249 AN: 3472

East Asian (EAS) AF: 0.0465 AC: 241 AN: 5178

South Asian (SAS) AF: 0.0780 AC: 376 AN: 4820

European-Finnish (FIN) AF: 0.0241 AC: 255 AN: 10580

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.0741 AC: 5040 AN: 68002

Other (OTH) AF: 0.0948 AC: 200 AN: 2110

Alfa AF: 0.0774 Hom.: 790

Bravo AF: 0.0772

Asia WGS AF: 0.0520 AC: 183 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	1.4
DANN	Benign	0.80
PhyloP100		0.17
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: rs742636; hg19: chr6-151096419; COSMIC: COSV62046188;