dbSNP rs2236661: PHLDB1:c.1827+28C>G (chr11-118628678-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001144758.3(PHLDB1):c.1827+28C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 1,581,766 control chromosomes in the GnomAD database, including 41,723 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 0.20 ( 3322 hom., cov: 33)

Exomes 𝑓: 0.23 ( 38401 hom. )

Consequence

PHLDB1
NM_001144758.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.527

Publications

17 publications found

Variant links:

Genes affected

PHLDB1 (HGNC:23697): (pleckstrin homology like domain family B member 1) Involved in regulation of embryonic development; regulation of epithelial to mesenchymal transition; and regulation of microtubule cytoskeleton organization. Located in basal cortex. [provided by Alliance of Genome Resources, Apr 2022]

PHLDB1 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=-0.88).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.345 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHLDB1	NM_001144758.3 link	c.1827+28C>G		intron_variant	Intron 6 of 22	ENST00000600882.6	NP_001138230.1	Q86UU1-1A0A024R3H6Q6ZUD6Q8NC75

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHLDB1	ENST00000600882.6 link	c.1827+28C>G		intron_variant	Intron 6 of 22	1	NM_001144758.3	ENSP00000469820.1		Q86UU1-1

Frequencies

GnomAD3 genomes

AF:

0.203

AC:

30825

AN:

152118

Hom.:

3319

Cov.:

show subpopulations

Gnomad AFR

AF:

0.123

Gnomad AMI

AF:

0.174

Gnomad AMR

AF:

0.237

Gnomad ASJ

AF:

0.201

Gnomad EAS

AF:

0.247

Gnomad SAS

AF:

0.357

Gnomad FIN

AF:

0.217

Gnomad MID

AF:

0.222

Gnomad NFE

AF:

0.227

Gnomad OTH

AF:

0.198

GnomAD2 exomes

AF:

0.237

AC:

45904

AN:

193578

AF XY:

0.245

show subpopulations

Gnomad AFR exome

AF:

0.119

Gnomad AMR exome

AF:

0.217

Gnomad ASJ exome

AF:

0.205

Gnomad EAS exome

AF:

0.252

Gnomad FIN exome

AF:

0.226

Gnomad NFE exome

AF:

0.227

Gnomad OTH exome

AF:

0.234

GnomAD4 exome

AF:

0.229

AC:

326927

AN:

1429530

Hom.:

38401

Cov.:

AF XY:

0.232

AC XY:

164925

AN XY:

709602

show subpopulations

African (AFR)

AF:

0.117

AC:

3792

AN:

32428

American (AMR)

AF:

0.215

AC:

8425

AN:

39110

Ashkenazi Jewish (ASJ)

AF:

0.203

AC:

5175

AN:

25438

East Asian (EAS)

AF:

0.222

AC:

8546

AN:

38510

South Asian (SAS)

AF:

0.339

AC:

28139

AN:

82960

European-Finnish (FIN)

AF:

0.221

AC:

10534

AN:

47590

Middle Eastern (MID)

AF:

0.222

AC:

1235

AN:

5562

European-Non Finnish (NFE)

AF:

0.225

AC:

247442

AN:

1098728

Other (OTH)

AF:

0.230

AC:

13639

AN:

59204

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

12885

25770

38656

51541

64426

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8612

17224

25836

34448

43060

<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:

0.203

AC:

30834

AN:

152236

Hom.:

3322

Cov.:

AF XY:

0.206

AC XY:

15348

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.123

AC:

5108

AN:

41560

American (AMR)

AF:

0.236

AC:

3617

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.201

AC:

697

AN:

3470

East Asian (EAS)

AF:

0.247

AC:

1274

AN:

5162

South Asian (SAS)

AF:

0.359

AC:

1731

AN:

4826

European-Finnish (FIN)

AF:

0.217

AC:

2296

AN:

10600

Middle Eastern (MID)

AF:

0.221

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.227

AC:

15465

AN:

67994

Other (OTH)

AF:

0.200

AC:

422

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1244

2489

3733

4978

6222

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

348

696

1044

1392

1740

<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:

0.210

Hom.:

656

Bravo

AF:

0.195

Asia WGS

AF:

0.273

AC:

947

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

3.8

(source)

DANN

Benign

0.49

PhyloP100

-0.53

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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