dbSNP rs2302350: PLEKHG6:c.1670+14G>A (chr12-6326587-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001384598.1(PLEKHG6):c.1670+14G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 1,450,664 control chromosomes in the GnomAD database, including 151,579 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 0.35 ( 11773 hom., cov: 31)

Exomes 𝑓: 0.46 ( 139806 hom. )

Consequence

PLEKHG6
NM_001384598.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0570

Publications

10 publications found

Variant links:

Genes affected

PLEKHG6 (HGNC:25562): (pleckstrin homology and RhoGEF domain containing G6) Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in regulation of small GTPase mediated signal transduction. Located in cell junction and centrosome. [provided by Alliance of Genome Resources, Apr 2022]

PLEKHG6 links:

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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=-0.84).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.48 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLEKHG6	NM_001384598.1 link	c.1670+14G>A		intron_variant	Intron 14 of 15	ENST00000684764.1	NP_001371527.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLEKHG6	ENST00000684764.1 link	c.1670+14G>A		intron_variant	Intron 14 of 15		NM_001384598.1	ENSP00000506982.1		Q3KR16-1

Frequencies

GnomAD3 genomes

AF:

0.353

AC:

53583

AN:

151964

Hom.:

11775

Cov.:

show subpopulations

Gnomad AFR

AF:

0.100

Gnomad AMI

AF:

0.409

Gnomad AMR

AF:

0.345

Gnomad ASJ

AF:

0.409

Gnomad EAS

AF:

0.184

Gnomad SAS

AF:

0.316

Gnomad FIN

AF:

0.586

Gnomad MID

AF:

0.357

Gnomad NFE

AF:

0.484

Gnomad OTH

AF:

0.338

GnomAD2 exomes

AF:

0.407

AC:

54549

AN:

133974

AF XY:

0.415

show subpopulations

Gnomad AFR exome

AF:

0.104

Gnomad AMR exome

AF:

0.325

Gnomad ASJ exome

AF:

0.402

Gnomad EAS exome

AF:

0.190

Gnomad FIN exome

AF:

0.569

Gnomad NFE exome

AF:

0.477

Gnomad OTH exome

AF:

0.411

GnomAD4 exome

AF:

0.456

AC:

592345

AN:

1298582

Hom.:

139806

Cov.:

AF XY:

0.455

AC XY:

289966

AN XY:

637886

show subpopulations

African (AFR)

AF:

0.0880

AC:

2334

AN:

26516

American (AMR)

AF:

0.311

AC:

6973

AN:

22438

Ashkenazi Jewish (ASJ)

AF:

0.397

AC:

7386

AN:

18602

East Asian (EAS)

AF:

0.224

AC:

7434

AN:

33220

South Asian (SAS)

AF:

0.334

AC:

20704

AN:

61944

European-Finnish (FIN)

AF:

0.574

AC:

26821

AN:

46750

Middle Eastern (MID)

AF:

0.355

AC:

1794

AN:

5060

European-Non Finnish (NFE)

AF:

0.482

AC:

497028

AN:

1031466

Other (OTH)

AF:

0.416

AC:

21871

AN:

52586

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

14651

29302

43954

58605

73256

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15218

30436

45654

60872

76090

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.352

AC:

53586

AN:

152082

Hom.:

11773

Cov.:

AF XY:

0.357

AC XY:

26538

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.100

AC:

4155

AN:

41508

American (AMR)

AF:

0.344

AC:

5265

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.409

AC:

1421

AN:

3472

East Asian (EAS)

AF:

0.184

AC:

950

AN:

5156

South Asian (SAS)

AF:

0.316

AC:

1518

AN:

4808

European-Finnish (FIN)

AF:

0.586

AC:

6191

AN:

10572

Middle Eastern (MID)

AF:

0.346

AC:

101

AN:

292

European-Non Finnish (NFE)

AF:

0.484

AC:

32897

AN:

67966

Other (OTH)

AF:

0.340

AC:

716

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1568

3136

4705

6273

7841

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

518

1036

1554

2072

2590

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.369

Hom.:

5180

Bravo

AF:

0.318

Asia WGS

AF:

0.263

AC:

914

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

4.1

(source)

DANN

Benign

0.71

PhyloP100

-0.057

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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