Variant chr11-77475278-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The XM_047427049.1(PAK1):c.-301-609T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 152,032 control chromosomes in the GnomAD database, including 6,770 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 0.29 ( 6769 hom., cov: 32)

Exomes 𝑓: 0.32 ( 1 hom. )

Consequence

PAK1
XM_047427049.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.108

Variant links:

Genes affected

PAK1 (HGNC:8590): (p21 (RAC1) activated kinase 1) This gene encodes a family member of serine/threonine p21-activating kinases, known as PAK proteins. These proteins are critical effectors that link RhoGTPases to cytoskeleton reorganization and nuclear signaling, and they serve as targets for the small GTP binding proteins Cdc42 and Rac. This specific family member regulates cell motility and morphology. Mutations in this gene have been associated with macrocephaly, seizures, and speech delay. Overexpression of this gene is also reported in many cancer types, and particularly in breast cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2020]

PAK1 links:

ENSG00000268635 (HGNC:):

ENSG00000268635 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Protein
PAK1	XM_047427049.1 link	c.-301-609T>G	intron_variant	XP_047283005.1
PAK1	XM_024448560.2 link	c.-301-609T>G	intron_variant	XP_024304328.1
PAK1	XM_047427054.1 link	c.-301-609T>G	intron_variant	XP_047283010.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000268635	ENST00000598970.2 link	n.1908A>C		non_coding_transcript_exon_variant	1/1	6

Frequencies

GnomAD3 genomes

AF:

0.291

AC:

44170

AN:

151880

Hom.:

6765

Cov.:

show subpopulations

Gnomad AFR

AF:

0.202

Gnomad AMI

AF:

0.304

Gnomad AMR

AF:

0.242

Gnomad ASJ

AF:

0.353

Gnomad EAS

AF:

0.242

Gnomad SAS

AF:

0.465

Gnomad FIN

AF:

0.287

Gnomad MID

AF:

0.293

Gnomad NFE

AF:

0.345

Gnomad OTH

AF:

0.299

GnomAD4 exome

AF:

0.324

AC:

AN:

Hom.:

Cov.:

AF XY:

0.222

AC XY:

AN XY:

show subpopulations

Gnomad4 FIN exome

AF:

0.500

Gnomad4 NFE exome

AF:

0.308

Gnomad4 OTH exome

AF:

0.333

GnomAD4 genome

AF:

0.291

AC:

44197

AN:

151998

Hom.:

6769

Cov.:

AF XY:

0.289

AC XY:

21481

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.202

Gnomad4 AMR

AF:

0.242

Gnomad4 ASJ

AF:

0.353

Gnomad4 EAS

AF:

0.242

Gnomad4 SAS

AF:

0.464

Gnomad4 FIN

AF:

0.287

Gnomad4 NFE

AF:

0.345

Gnomad4 OTH

AF:

0.299

Alfa

AF:

0.313

Hom.:

2088

Bravo

AF:

0.280

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

4.8

DANN

Benign

0.73

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over