dbSNP rs17748: PHLDB1:n.4931C>T (chr11-118657714-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000532517.5(PHLDB1):n.4931C>T 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 0.189 in 156,122 control chromosomes in the GnomAD database, including 3,184 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 0.19 ( 3088 hom., cov: 32)

Exomes 𝑓: 0.20 ( 96 hom. )

Consequence

PHLDB1
ENST00000532517.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0940

Publications

28 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:

TREH (HGNC:12266): (trehalase) This gene encodes an enzyme that hydrolyses trehalose, a disaccharide formed from two glucose molecules found mainly in fungi, plants, and insects. A partial duplication of this gene is located adjacent to this locus on chromosome 11. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2014]

TREH Gene-Disease associations (from GenCC):

diarrhea-vomiting due to trehalase deficiency
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

TREH 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=-0.8).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHLDB1	NM_001144758.3 link	c.*891C>T		3_prime_UTR_variant	Exon 23 of 23	ENST00000600882.6	NP_001138230.1
TREH	NM_007180.3 link	c.*575G>A		3_prime_UTR_variant	Exon 15 of 15	ENST00000264029.9	NP_009111.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHLDB1	ENST00000600882.6 link	c.*891C>T		3_prime_UTR_variant	Exon 23 of 23	1	NM_001144758.3	ENSP00000469820.1
TREH	ENST00000264029.9 link	c.*575G>A		3_prime_UTR_variant	Exon 15 of 15	1	NM_007180.3	ENSP00000264029.5

Frequencies

GnomAD3 genomes

AF:

0.189

AC:

28680

AN:

152014

Hom.:

3086

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0763

Gnomad AMI

AF:

0.171

Gnomad AMR

AF:

0.229

Gnomad ASJ

AF:

0.200

Gnomad EAS

AF:

0.243

Gnomad SAS

AF:

0.356

Gnomad FIN

AF:

0.217

Gnomad MID

AF:

0.222

Gnomad NFE

AF:

0.227

Gnomad OTH

AF:

0.187

GnomAD4 exome

AF:

0.197

AC:

785

AN:

3990

Hom.:

Cov.:

AF XY:

0.199

AC XY:

435

AN XY:

2182

show subpopulations

African (AFR)

AF:

0.0333

AC:

AN:

American (AMR)

AF:

0.164

AC:

136

AN:

828

Ashkenazi Jewish (ASJ)

AF:

0.357

AC:

AN:

East Asian (EAS)

AF:

0.145

AC:

AN:

South Asian (SAS)

AF:

0.352

AC:

AN:

182

European-Finnish (FIN)

AF:

0.214

AC:

AN:

426

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.198

AC:

457

AN:

2308

Other (OTH)

AF:

0.157

AC:

AN:

140

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

101

134

168

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.189

AC:

28688

AN:

152132

Hom.:

3088

Cov.:

AF XY:

0.193

AC XY:

14321

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.0762

AC:

3165

AN:

41512

American (AMR)

AF:

0.228

AC:

3493

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.200

AC:

694

AN:

3470

East Asian (EAS)

AF:

0.243

AC:

1254

AN:

5158

South Asian (SAS)

AF:

0.358

AC:

1724

AN:

4822

European-Finnish (FIN)

AF:

0.217

AC:

2294

AN:

10590

Middle Eastern (MID)

AF:

0.221

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.227

AC:

15445

AN:

67980

Other (OTH)

AF:

0.189

AC:

399

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1139

2279

3418

4558

5697

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

324

648

972

1296

1620

<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:

0.216

Hom.:

6715

Bravo

AF:

0.179

Asia WGS

AF:

0.266

AC:

924

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

1.9

(source)

DANN

Benign

0.72

PhyloP100

0.094

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

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

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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