rs10892247

Variant names:

• chr11-118619361-G-A
• rs10892247
• NM_001144758.3:c.355+3150G>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.355+3150G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 152,140 control chromosomes in the GnomAD database, including 3,045 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 (3045 hom., cov: 32)
• Consequence: PHLDB1 NM_001144758.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.222
• Publications: 10 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=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.34 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHLDB1	NM_001144758.3	c.355+3150G>A		intron_variant	Intron 4 of 22	ENST00000600882.6	NP_001138230.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHLDB1	ENST00000600882.6	c.355+3150G>A		intron_variant	Intron 4 of 22	1	NM_001144758.3	ENSP00000469820.1

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28428 AN: 152022 Hom.: 3043 Cov.: 32

Gnomad AFR AF: 0.0762

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.200

Gnomad EAS AF: 0.223

Gnomad SAS AF: 0.352

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.187

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

GnomAD4 genome AF: 0.187 AC: 28439 AN: 152140 Hom.: 3045 Cov.: 32 AF XY: 0.191 AC XY: 14179 AN XY: 74372

African (AFR) AF: 0.0762 AC: 3162 AN: 41500

American (AMR) AF: 0.228 AC: 3480 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.200 AC: 692 AN: 3468

East Asian (EAS) AF: 0.223 AC: 1155 AN: 5178

South Asian (SAS) AF: 0.354 AC: 1705 AN: 4820

European-Finnish (FIN) AF: 0.216 AC: 2289 AN: 10594

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.226 AC: 15336 AN: 67982

Other (OTH) AF: 0.189 AC: 398 AN: 2108

Alfa AF: 0.196 Hom.: 437

Bravo AF: 0.177

Asia WGS AF: 0.258 AC: 894 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.4
DANN	Benign	0.53
PhyloP100		0.22
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: rs10892247; hg19: chr11-118490076;