chr11-118657714-C-T

Variant names:

• chr11-118657714-C-T
• rs17748
• ENST00000532517.5:n.4931C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000532517.5(PHLDB1):​n.4931C>T variant causes a non coding transcript exon 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 ENST00000532517.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0940
• Publications: 28 publications found

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]

TREH Gene-Disease associations (from GenCC):

• diarrhea-vomiting due to trehalase deficiency

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000532517.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHLDB1	NM_001144758.3	MANE Select	c.*891C>T		3_prime_UTR	Exon 23 of 23	NP_001138230.1
	TREH	NM_007180.3	MANE Select	c.*575G>A		3_prime_UTR	Exon 15 of 15	NP_009111.2
	PHLDB1	NM_015157.4		c.*891C>T		3_prime_UTR	Exon 24 of 24	NP_055972.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHLDB1	ENST00000532517.5	TSL:1	n.4931C>T		non_coding_transcript_exon	Exon 18 of 18
	PHLDB1	ENST00000614369.4	TSL:1	n.3128C>T		non_coding_transcript_exon	Exon 16 of 16
	PHLDB1	ENST00000600882.6	TSL:1 MANE Select	c.*891C>T		3_prime_UTR	Exon 23 of 23	ENSP00000469820.1

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

African (AFR) AF: 0.0333 AC: 1 AN: 30

American (AMR) AF: 0.164 AC: 136 AN: 828

Ashkenazi Jewish (ASJ) AF: 0.357 AC: 5 AN: 14

East Asian (EAS) AF: 0.145 AC: 9 AN: 62

South Asian (SAS) AF: 0.352 AC: 64 AN: 182

European-Finnish (FIN) AF: 0.214 AC: 91 AN: 426

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.198 AC: 457 AN: 2308

Other (OTH) AF: 0.157 AC: 22 AN: 140

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

African (AFR) AF: 0.0762 AC: 3165 AN: 41512

American (AMR) AF: 0.228 AC: 3493 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.200 AC: 694 AN: 3470

East Asian (EAS) AF: 0.243 AC: 1254 AN: 5158

South Asian (SAS) AF: 0.358 AC: 1724 AN: 4822

European-Finnish (FIN) AF: 0.217 AC: 2294 AN: 10590

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.227 AC: 15445 AN: 67980

Other (OTH) AF: 0.189 AC: 399 AN: 2108

Alfa AF: 0.216 Hom.: 6715

Bravo AF: 0.179

Asia WGS AF: 0.266 AC: 924 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.9
DANN	Benign	0.72
PhyloP100		0.094
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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