chr3-111919285-A-C

Position:

• chr3-111919285-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000431670.7(PHLDB2):​c.1863+70A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.881 in 1,531,756 control chromosomes in the GnomAD database, including 595,875 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 0.86 (56961 hom., cov: 32)
  • Exomes 𝑓: 0.88 (538914 hom.)
• Consequence: PHLDB2 ENST00000431670.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.556

Genes affected

PHLDB2 (HGNC:29573): (pleckstrin homology like domain family B member 2) Enables cadherin binding activity. Involved in several processes, including negative regulation of focal adhesion assembly; regulation of cytoskeleton organization; and regulation of embryonic development. Located in several cellular components, including basal cortex; cell leading edge; and intermediate filament cytoskeleton. Colocalizes with focal adhesion. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.884 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHLDB2	NM_001134438.2	c.1863+70A>C		intron_variant		ENST00000431670.7	NP_001127910.1
PHLDB2	NM_001134437.2	c.1944+70A>C		intron_variant			NP_001127909.1
PHLDB2	NM_001134439.2	c.1863+70A>C		intron_variant			NP_001127911.1
PHLDB2	NM_145753.2	c.1863+70A>C		intron_variant			NP_665696.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PHLDB2	ENST00000431670.7	c.1863+70A>C		intron_variant		1	NM_001134438.2	ENSP00000405405	P3

Frequencies

GnomAD3 genomes AF: 0.864 AC: 131388 AN: 152098 Hom.: 56944 Cov.: 32

Gnomad AFR AF: 0.802

Gnomad AMI AF: 0.930

Gnomad AMR AF: 0.876

Gnomad ASJ AF: 0.967

Gnomad EAS AF: 0.899

Gnomad SAS AF: 0.759

Gnomad FIN AF: 0.909

Gnomad MID AF: 0.930

Gnomad NFE AF: 0.890

Gnomad OTH AF: 0.874

GnomAD4 exome AF: 0.883 AC: 1217847 AN: 1379540 Hom.: 538914 AF XY: 0.880 AC XY: 607308 AN XY: 690054

Gnomad4 AFR exome AF: 0.798

Gnomad4 AMR exome AF: 0.881

Gnomad4 ASJ exome AF: 0.962

Gnomad4 EAS exome AF: 0.935

Gnomad4 SAS exome AF: 0.770

Gnomad4 FIN exome AF: 0.902

Gnomad4 NFE exome AF: 0.890

Gnomad4 OTH exome AF: 0.879

GnomAD4 genome AF: 0.864 AC: 131452 AN: 152216 Hom.: 56961 Cov.: 32 AF XY: 0.865 AC XY: 64357 AN XY: 74418

Gnomad4 AFR AF: 0.801

Gnomad4 AMR AF: 0.875

Gnomad4 ASJ AF: 0.967

Gnomad4 EAS AF: 0.900

Gnomad4 SAS AF: 0.759

Gnomad4 FIN AF: 0.909

Gnomad4 NFE AF: 0.890

Gnomad4 OTH AF: 0.870

Alfa AF: 0.880 Hom.: 15808

Bravo AF: 0.860

Asia WGS AF: 0.790 AC: 2746 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.9
DANN	Benign	0.50

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

LitVar

Other links and lift over

dbSNP: rs951660; hg19: chr3-111638132; COSMIC: COSV67309266; COSMIC: COSV67309266;