rs2236661

Positions:

• chr11-118628678-C-G

Variant summary

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

The NM_001144758.3(PHLDB1):​c.1827+28C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 1,581,766 control chromosomes in the GnomAD database, including 41,723 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 0.20 (3322 hom., cov: 33)
  • Exomes 𝑓: 0.23 (38401 hom.)
• Consequence: PHLDB1 NM_001144758.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.527

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.345 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHLDB1	NM_001144758.3	c.1827+28C>G		intron_variant		ENST00000600882.6	NP_001138230.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PHLDB1	ENST00000600882.6	c.1827+28C>G		intron_variant		1	NM_001144758.3	ENSP00000469820.1

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30825 AN: 152118 Hom.: 3319 Cov.: 33

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.247

Gnomad SAS AF: 0.357

Gnomad FIN AF: 0.217

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.198

GnomAD3 exomes AF: 0.237 AC: 45904 AN: 193578 Hom.: 5523 AF XY: 0.245 AC XY: 26262 AN XY: 107182

Gnomad AFR exome AF: 0.119

Gnomad AMR exome AF: 0.217

Gnomad ASJ exome AF: 0.205

Gnomad EAS exome AF: 0.252

Gnomad SAS exome AF: 0.347

Gnomad FIN exome AF: 0.226

Gnomad NFE exome AF: 0.227

Gnomad OTH exome AF: 0.234

GnomAD4 exome AF: 0.229 AC: 326927 AN: 1429530 Hom.: 38401 Cov.: 32 AF XY: 0.232 AC XY: 164925 AN XY: 709602

Gnomad4 AFR exome AF: 0.117

Gnomad4 AMR exome AF: 0.215

Gnomad4 ASJ exome AF: 0.203

Gnomad4 EAS exome AF: 0.222

Gnomad4 SAS exome AF: 0.339

Gnomad4 FIN exome AF: 0.221

Gnomad4 NFE exome AF: 0.225

Gnomad4 OTH exome AF: 0.230

GnomAD4 genome AF: 0.203 AC: 30834 AN: 152236 Hom.: 3322 Cov.: 33 AF XY: 0.206 AC XY: 15348 AN XY: 74424

Gnomad4 AFR AF: 0.123

Gnomad4 AMR AF: 0.236

Gnomad4 ASJ AF: 0.201

Gnomad4 EAS AF: 0.247

Gnomad4 SAS AF: 0.359

Gnomad4 FIN AF: 0.217

Gnomad4 NFE AF: 0.227

Gnomad4 OTH AF: 0.200

Alfa AF: 0.210 Hom.: 656

Bravo AF: 0.195

Asia WGS AF: 0.273 AC: 947 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.8
DANN	Benign	0.49
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2236661; hg19: chr11-118499394; COSMIC: COSV61877152; COSMIC: COSV61877152;