Genetic Variant PHLDB1:c.-106G>A (chr11-118607615-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_001144758.3(PHLDB1):c.-106G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.411 in 144,560 control chromosomes in the GnomAD database, including 13,259 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 0.41 ( 13254 hom., cov: 23)

Exomes 𝑓: 0.16 ( 5 hom. )

Consequence

PHLDB1
NM_001144758.3 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0570

Publications

20 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:

LOC124902765 (HGNC:):

LOC124902765 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=-0.67).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.582 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001144758.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PHLDB1	NM_001144758.3	MANE Select	c.-106G>A	5_prime_UTR	Exon 1 of 23	NP_001138230.1
PHLDB1	NM_001144759.3		c.-106G>A	5_prime_UTR	Exon 1 of 21	NP_001138231.1
PHLDB1	NM_015157.4		c.-179+943G>A	intron	N/A	NP_055972.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PHLDB1	ENST00000600882.6	TSL:1 MANE Select	c.-106G>A	5_prime_UTR	Exon 1 of 23	ENSP00000469820.1
PHLDB1	ENST00000361417.6	TSL:1	c.-179+943G>A	intron	N/A	ENSP00000354498.2
PHLDB1	ENST00000530994.5	TSL:2	n.-263G>A	non_coding_transcript_exon	Exon 1 of 22	ENSP00000431508.1

Frequencies

GnomAD3 genomes

AF:

0.411

AC:

59312

AN:

144238

Hom.:

13234

Cov.:

show subpopulations

Gnomad AFR

AF:

0.589

Gnomad AMI

AF:

0.300

Gnomad AMR

AF:

0.286

Gnomad ASJ

AF:

0.395

Gnomad EAS

AF:

0.302

Gnomad SAS

AF:

0.459

Gnomad FIN

AF:

0.287

Gnomad MID

AF:

0.432

Gnomad NFE

AF:

0.363

Gnomad OTH

AF:

0.406

GnomAD4 exome

AF:

0.160

AC:

AN:

212

Hom.:

Cov.:

AF XY:

0.141

AC XY:

AN XY:

142

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AF:

0.167

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.0625

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AF:

1.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.155

AC:

AN:

168

Other (OTH)

AF:

0.0714

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

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:

0.411

AC:

59363

AN:

144348

Hom.:

13254

Cov.:

AF XY:

0.408

AC XY:

28543

AN XY:

70006

show subpopulations

African (AFR)

AF:

0.589

AC:

22244

AN:

37786

American (AMR)

AF:

0.286

AC:

4182

AN:

14638

Ashkenazi Jewish (ASJ)

AF:

0.395

AC:

1353

AN:

3428

East Asian (EAS)

AF:

0.303

AC:

1455

AN:

4808

South Asian (SAS)

AF:

0.458

AC:

2064

AN:

4510

European-Finnish (FIN)

AF:

0.287

AC:

2644

AN:

9220

Middle Eastern (MID)

AF:

0.421

AC:

117

AN:

278

European-Non Finnish (NFE)

AF:

0.363

AC:

24213

AN:

66780

Other (OTH)

AF:

0.410

AC:

823

AN:

2008

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

1375

2749

4124

5498

6873

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

550

1100

1650

2200

2750

<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:

0.383

Hom.:

4696

Bravo

AF:

0.429

Asia WGS

AF:

0.433

AC:

1495

AN:

3450

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

(source)

DANN

Benign

0.76

PhyloP100

-0.057

PromoterAI

0.15

Neutral

(source)

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over