dbSNP rs7109645: ENSG00000268635:n.1908A>C (chr11-77475278-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000598970.2(ENSG00000268635):n.1908A>C variant causes a non coding transcript exon 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

ENSG00000268635
ENST00000598970.2 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.108

Publications

5 publications found

Variant links:

Genes affected

ENSG00000268635 (HGNC:):

ENSG00000268635 links:

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 Gene-Disease associations (from GenCC):

intellectual developmental disorder with macrocephaly, seizures, and speech delay
Inheritance: AD Classification: STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

PAK1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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	Exon rank	Protein
PAK1	XM_047427049.1 link	c.-301-609T>G	intron_variant	Intron 1 of 16	XP_047283005.1
PAK1	XM_024448560.2 link	c.-301-609T>G	intron_variant	Intron 2 of 16	XP_024304328.1
PAK1	XM_047427054.1 link	c.-301-609T>G	intron_variant	Intron 1 of 15	XP_047283010.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000268635	ENST00000598970.2 link	n.1908A>C		non_coding_transcript_exon_variant	Exon 1 of 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

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.308

AC:

AN:

Other (OTH)

AF:

0.333

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.291

AC:

44197

AN:

151998

Hom.:

6769

Cov.:

AF XY:

0.289

AC XY:

21481

AN XY:

74314

show subpopulations

African (AFR)

AF:

0.202

AC:

8360

AN:

41430

American (AMR)

AF:

0.242

AC:

3686

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.353

AC:

1224

AN:

3470

East Asian (EAS)

AF:

0.242

AC:

1250

AN:

5172

South Asian (SAS)

AF:

0.464

AC:

2235

AN:

4818

European-Finnish (FIN)

AF:

0.287

AC:

3033

AN:

10572

Middle Eastern (MID)

AF:

0.288

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.345

AC:

23415

AN:

67964

Other (OTH)

AF:

0.299

AC:

633

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1580

3161

4741

6322

7902

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.315

Hom.:

12386

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

(source)

DANN

Benign

0.73

PhyloP100

-0.11

Splicing

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

Publications

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rs7109645

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over