11-118618067-A-C

Position:

• chr11-118618067-A-C

Variant summary

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

The NM_001144758.3(PHLDB1):​c.355+1856A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 151,876 control chromosomes in the GnomAD database, including 3,799 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 0.22 (3799 hom., cov: 31)
• Consequence: PHLDB1 NM_001144758.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0360

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=-0.77).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.346 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PHLDB1	NM_001144758.3	c.355+1856A>C		intron_variant		ENST00000600882.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHLDB1	ENST00000600882.6	c.355+1856A>C		intron_variant		1	NM_001144758.3

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33685 AN: 151758 Hom.: 3793 Cov.: 31

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.248

Gnomad SAS AF: 0.358

Gnomad FIN AF: 0.217

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.212

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

GnomAD4 genome AF: 0.222 AC: 33708 AN: 151876 Hom.: 3799 Cov.: 31 AF XY: 0.224 AC XY: 16629 AN XY: 74234

Gnomad4 AFR AF: 0.187

Gnomad4 AMR AF: 0.246

Gnomad4 ASJ AF: 0.206

Gnomad4 EAS AF: 0.248

Gnomad4 SAS AF: 0.360

Gnomad4 FIN AF: 0.217

Gnomad4 NFE AF: 0.229

Gnomad4 OTH AF: 0.214

Alfa AF: 0.230 Hom.: 4492

Bravo AF: 0.216

Asia WGS AF: 0.280 AC: 973 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	5.8
DANN	Benign	0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs11216930; hg19: chr11-118488782;