11-118615395-G-A

Variant names:

• chr11-118615395-G-A
• rs45540840
• NM_001144758.3:c.185-646G>A

Variant summary

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

The NM_001144758.3(PHLDB1):​c.185-646G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 151,938 control chromosomes in the GnomAD database, including 3,576 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 0.21 (3576 hom., cov: 31)
• Consequence: PHLDB1 NM_001144758.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.691
• Publications: 9 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.349 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001144758.3. 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.185-646G>A		intron	N/A	NP_001138230.1
	PHLDB1	NM_015157.4		c.185-646G>A		intron	N/A	NP_055972.1
	PHLDB1	NM_001144759.3		c.185-646G>A		intron	N/A	NP_001138231.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHLDB1	ENST00000600882.6	TSL:1 MANE Select	c.185-646G>A		intron	N/A	ENSP00000469820.1
	PHLDB1	ENST00000361417.6	TSL:1	c.185-646G>A		intron	N/A	ENSP00000354498.2
	PHLDB1	ENST00000356063.9	TSL:2	c.185-646G>A		intron	N/A	ENSP00000348359.5

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32564 AN: 151820 Hom.: 3572 Cov.: 31

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.267

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.217

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.206

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

GnomAD4 genome AF: 0.214 AC: 32582 AN: 151938 Hom.: 3576 Cov.: 31 AF XY: 0.217 AC XY: 16145 AN XY: 74254

African (AFR) AF: 0.162 AC: 6732 AN: 41434

American (AMR) AF: 0.243 AC: 3715 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 702 AN: 3470

East Asian (EAS) AF: 0.267 AC: 1372 AN: 5144

South Asian (SAS) AF: 0.364 AC: 1748 AN: 4808

European-Finnish (FIN) AF: 0.217 AC: 2288 AN: 10552

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.226 AC: 15359 AN: 67946

Other (OTH) AF: 0.208 AC: 440 AN: 2114

Alfa AF: 0.214 Hom.: 771

Bravo AF: 0.208

Asia WGS AF: 0.299 AC: 1038 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	9.7
DANN	Benign	0.77
PhyloP100		-0.69
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs45540840; hg19: chr11-118486110;