rs12419235

Variant names:

• chr11-118635839-G-T
• rs12419235
• NM_001144758.3:c.2535+291G>T

Variant summary

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

The NM_001144758.3(PHLDB1):​c.2535+291G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0153 in 152,336 control chromosomes in the GnomAD database, including 149 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 0.015 (149 hom., cov: 32)
• Consequence: PHLDB1 NM_001144758.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.30

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHLDB1	NM_001144758.3	c.2535+291G>T		intron_variant	Intron 10 of 22	ENST00000600882.6	NP_001138230.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHLDB1	ENST00000600882.6	c.2535+291G>T		intron_variant	Intron 10 of 22	1	NM_001144758.3	ENSP00000469820.1

Frequencies

GnomAD3 genomes AF: 0.0153 AC: 2333 AN: 152218 Hom.: 149 Cov.: 32

Gnomad AFR AF: 0.00285

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0766

Gnomad ASJ AF: 0.0107

Gnomad EAS AF: 0.157

Gnomad SAS AF: 0.00724

Gnomad FIN AF: 0.000471

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00182

Gnomad OTH AF: 0.0148

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0153 AC: 2328 AN: 152336 Hom.: 149 Cov.: 32 AF XY: 0.0165 AC XY: 1229 AN XY: 74492

Gnomad4 AFR AF: 0.00284

Gnomad4 AMR AF: 0.0765

Gnomad4 ASJ AF: 0.0107

Gnomad4 EAS AF: 0.157

Gnomad4 SAS AF: 0.00683

Gnomad4 FIN AF: 0.000471

Gnomad4 NFE AF: 0.00182

Gnomad4 OTH AF: 0.0147

Alfa AF: 0.0247 Hom.: 44

Bravo AF: 0.0253

Asia WGS AF: 0.0550 AC: 192 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.9
DANN	Benign	0.57

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: rs12419235; hg19: chr11-118506557;