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

Variant summary

Our verdict is Benign. Variant got -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

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein	UniProt
PHLDB1	NM_015157.4 link	c.-199A>G	5_prime_UTR_variant	Exon 1 of 24	NP_055972.1	Q86UU1-1A0A024R3H6Q6ZUD6
PHLDB1	XM_011542709.3 link	c.-42A>G	5_prime_UTR_variant	Exon 1 of 27	XP_011541011.1
LOC124902765	XR_007062908.1 link	n.926T>C	non_coding_transcript_exon_variant	Exon 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHLDB1	ENST00000361417 link	c.-199A>G		5_prime_UTR_variant	Exon 1 of 24	1		ENSP00000354498.2		Q86UU1-1

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

Gnomad4 AFR exome

AF:

0.875

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.500

Gnomad4 FIN exome

AF:

0.600

Gnomad4 NFE exome

AF:

0.788

Gnomad4 OTH exome

AF:

0.667

GnomAD4 genome

AF:

0.748

AC:

113756

AN:

152082

Hom.:

43102

Cov.:

AF XY:

0.745

AC XY:

55344

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.886

Gnomad4 AMR

AF:

0.732

Gnomad4 ASJ

AF:

0.759

Gnomad4 EAS

AF:

0.738

Gnomad4 SAS

AF:

0.631

Gnomad4 FIN

AF:

0.668

Gnomad4 NFE

AF:

0.688

Gnomad4 OTH

AF:

0.747

Alfa

AF:

0.703

Hom.:

59758

Bravo

AF:

0.765

Asia WGS

AF:

0.712

AC:

2480

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Benign

0.74

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over