Genetic Variant PHLDB1:c.-199A>G (chr11-118606652-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_015157.4(PHLDB1):c.-199A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.748 in 152,186 control chromosomes in the GnomAD database, including 43,132 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 0.75 ( 43102 hom., cov: 31)

Exomes 𝑓: 0.77 ( 30 hom. )

Consequence

PHLDB1
NM_015157.4 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.64

Publications

99 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 Gene-Disease associations (from GenCC):

osteogenesis imperfecta, type 23
Inheritance: AR Classification: MODERATE Submitted by: PanelApp Australia

PHLDB1 links:

LOC124902765 (HGNC:):

LOC124902765 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_015157.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.62).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.878 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015157.4. 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
	PHLDB1	NM_015157.4		c.-199A>G		5_prime_UTR	Exon 1 of 24	NP_055972.1	Q86UU1-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PHLDB1	ENST00000361417.6	TSL:1	c.-199A>G	5_prime_UTR	Exon 1 of 24	ENSP00000354498.2	Q86UU1-1
PHLDB1	ENST00000860943.1		c.-42A>G	5_prime_UTR	Exon 1 of 22	ENSP00000531002.1
PHLDB1	ENST00000860941.1		c.-42A>G	5_prime_UTR	Exon 1 of 21	ENSP00000531000.1

Frequencies

GnomAD3 genomes

AF:

0.748

AC:

113646

AN:

151964

Hom.:

43050

Cov.:

show subpopulations

Gnomad AFR

AF:

0.886

Gnomad AMI

AF:

0.769

Gnomad AMR

AF:

0.732

Gnomad ASJ

AF:

0.759

Gnomad EAS

AF:

0.738

Gnomad SAS

AF:

0.632

Gnomad FIN

AF:

0.668

Gnomad MID

AF:

0.769

Gnomad NFE

AF:

0.688

Gnomad OTH

AF:

0.746

GnomAD4 exome

AF:

0.769

AC:

AN:

104

Hom.:

Cov.:

AF XY:

0.782

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.875

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AF:

0.600

AC:

AN:

Middle Eastern (MID)

AF:

1.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.788

AC:

AN:

Other (OTH)

AF:

0.667

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

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:

0.748

AC:

113756

AN:

152082

Hom.:

43102

Cov.:

AF XY:

0.745

AC XY:

55344

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.886

AC:

36772

AN:

41500

American (AMR)

AF:

0.732

AC:

11185

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.759

AC:

2632

AN:

3470

East Asian (EAS)

AF:

0.738

AC:

3819

AN:

5172

South Asian (SAS)

AF:

0.631

AC:

3039

AN:

4818

European-Finnish (FIN)

AF:

0.668

AC:

7050

AN:

10552

Middle Eastern (MID)

AF:

0.769

AC:

226

AN:

294

European-Non Finnish (NFE)

AF:

0.688

AC:

46754

AN:

67968

Other (OTH)

AF:

0.747

AC:

1578

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1458

2916

4374

5832

7290

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

840

1680

2520

3360

4200

<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:

0.713

Hom.:

154622

Bravo

AF:

0.765

Asia WGS

AF:

0.712

AC:

2480

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

(source)

DANN

Benign

0.74

PhyloP100

1.6

PromoterAI

-0.041

Neutral

(source)

Mutation Taster

=297/3

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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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