rs17748

Positions:

• chr11-118657714-C-T

Variant summary

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

The NM_001144758.3(PHLDB1):​c.*891C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 156,122 control chromosomes in the GnomAD database, including 3,184 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 0.19 (3088 hom., cov: 32)
  • Exomes 𝑓: 0.20 (96 hom.)
• Consequence: PHLDB1 NM_001144758.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0940

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]

TREH (HGNC:12266): (trehalase) This gene encodes an enzyme that hydrolyses trehalose, a disaccharide formed from two glucose molecules found mainly in fungi, plants, and insects. A partial duplication of this gene is located adjacent to this locus on chromosome 11. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHLDB1	NM_001144758.3	c.*891C>T		3_prime_UTR_variant	23/23	ENST00000600882.6	NP_001138230.1
TREH	NM_007180.3	c.*575G>A		3_prime_UTR_variant	15/15	ENST00000264029.9	NP_009111.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TREH	ENST00000264029.9	c.*575G>A		3_prime_UTR_variant	15/15	1	NM_007180.3	ENSP00000264029	P1
PHLDB1	ENST00000600882.6	c.*891C>T		3_prime_UTR_variant	23/23	1	NM_001144758.3	ENSP00000469820

Frequencies

GnomAD3 genomes AF: 0.189 AC: 28680 AN: 152014 Hom.: 3086 Cov.: 32

Gnomad AFR AF: 0.0763

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.200

Gnomad EAS AF: 0.243

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.217

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.187

GnomAD4 exome AF: 0.197 AC: 785 AN: 3990 Hom.: 96 Cov.: 0 AF XY: 0.199 AC XY: 435 AN XY: 2182

Gnomad4 AFR exome AF: 0.0333

Gnomad4 AMR exome AF: 0.164

Gnomad4 ASJ exome AF: 0.357

Gnomad4 EAS exome AF: 0.145

Gnomad4 SAS exome AF: 0.352

Gnomad4 FIN exome AF: 0.214

Gnomad4 NFE exome AF: 0.198

Gnomad4 OTH exome AF: 0.157

GnomAD4 genome AF: 0.189 AC: 28688 AN: 152132 Hom.: 3088 Cov.: 32 AF XY: 0.193 AC XY: 14321 AN XY: 74374

Gnomad4 AFR AF: 0.0762

Gnomad4 AMR AF: 0.228

Gnomad4 ASJ AF: 0.200

Gnomad4 EAS AF: 0.243

Gnomad4 SAS AF: 0.358

Gnomad4 FIN AF: 0.217

Gnomad4 NFE AF: 0.227

Gnomad4 OTH AF: 0.189

Alfa AF: 0.221 Hom.: 4857

Bravo AF: 0.179

Asia WGS AF: 0.266 AC: 924 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.9
DANN	Benign	0.72
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Other links and lift over

dbSNP: rs17748; hg19: chr11-118528424; COSMIC: COSV50621127; COSMIC: COSV50621127;