dbSNP rs143684449: PLEKHD1:c.244-10T>C (chr14-69500567-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001161498.2(PLEKHD1):c.244-10T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00299 in 1,544,800 control chromosomes in the GnomAD database, including 127 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 64 hom., cov: 33)

Exomes 𝑓: 0.0016 ( 63 hom. )

Consequence

PLEKHD1
NM_001161498.2 intron

Scores

Splicing: ADA: 0.03670

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.92

Publications

0 publications found

Variant links:

Genes affected

PLEKHD1 (HGNC:20148): (pleckstrin homology and coiled-coil domain containing D1)

PLEKHD1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 14-69500567-T-C is Benign according to our data. Variant chr14-69500567-T-C is described in ClinVar as Benign. ClinVar VariationId is 785462.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0527 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001161498.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLEKHD1	NM_001161498.2	MANE Select	c.244-10T>C		intron	N/A	NP_001154970.1	A6NEE1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PLEKHD1	ENST00000322564.9	TSL:1 MANE Select	c.244-10T>C	intron	N/A	ENSP00000317175.7	A6NEE1
PLEKHD1	ENST00000923232.1		c.244-10T>C	intron	N/A	ENSP00000593291.1
PLEKHD1	ENST00000556123.1	TSL:2	n.876T>C	non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.0158

AC:

2400

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0546

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00517

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000324

Gnomad OTH

AF:

0.0167

GnomAD2 exomes

AF:

0.00416

AC:

616

AN:

147910

AF XY:

0.00341

show subpopulations

Gnomad AFR exome

AF:

0.0638

Gnomad AMR exome

AF:

0.00373

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000264

Gnomad OTH exome

AF:

0.00193

GnomAD4 exome

AF:

0.00159

AC:

2210

AN:

1392554

Hom.:

Cov.:

AF XY:

0.00144

AC XY:

991

AN XY:

686472

show subpopulations

African (AFR)

AF:

0.0553

AC:

1738

AN:

31420

American (AMR)

AF:

0.00407

AC:

142

AN:

34880

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24560

East Asian (EAS)

AF:

0.00

AC:

AN:

35704

South Asian (SAS)

AF:

0.000128

AC:

AN:

78148

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48912

Middle Eastern (MID)

AF:

0.00195

AC:

AN:

5638

European-Non Finnish (NFE)

AF:

0.000107

AC:

115

AN:

1075602

Other (OTH)

AF:

0.00336

AC:

194

AN:

57690

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

107

215

322

430

537

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

116

174

232

290

<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:

0.0158

AC:

2407

AN:

152246

Hom.:

Cov.:

AF XY:

0.0155

AC XY:

1152

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.0546

AC:

2268

AN:

41538

American (AMR)

AF:

0.00516

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.000207

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000324

AC:

AN:

67992

Other (OTH)

AF:

0.0166

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

116

232

348

464

580

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

<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:

0.0127

Hom.:

Bravo

AF:

0.0185

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

(source)

DANN

Benign

0.84

PhyloP100

1.9

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.037

dbscSNV1_RF

Benign

0.28

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over