rs10892248

Variant names:

• chr11-118630305-G-A
• rs10892248
• NM_001144758.3:c.1828-902G>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.1828-902G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 152,108 control chromosomes in the GnomAD database, including 3,395 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 0.20 (3395 hom., cov: 31)
• Consequence: PHLDB1 NM_001144758.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.99
• 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=-0.7).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.35 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHLDB1	NM_001144758.3	MANE Select	c.1828-902G>A		intron	N/A	NP_001138230.1	Q86UU1-1
	PHLDB1	NM_015157.4		c.1828-902G>A		intron	N/A	NP_055972.1	Q86UU1-1
	PHLDB1	NM_001144759.3		c.1828-902G>A		intron	N/A	NP_001138231.1	Q86UU1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHLDB1	ENST00000600882.6	TSL:1 MANE Select	c.1828-902G>A		intron	N/A	ENSP00000469820.1	Q86UU1-1
	PHLDB1	ENST00000361417.6	TSL:1	c.1828-902G>A		intron	N/A	ENSP00000354498.2	Q86UU1-1
	PHLDB1	ENST00000532517.5	TSL:1	n.1722-902G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.204 AC: 31034 AN: 151990 Hom.: 3392 Cov.: 31

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.203

Gnomad EAS AF: 0.288

Gnomad SAS AF: 0.364

Gnomad FIN AF: 0.217

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.199

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

GnomAD4 genome AF: 0.204 AC: 31042 AN: 152108 Hom.: 3395 Cov.: 31 AF XY: 0.208 AC XY: 15456 AN XY: 74346

African (AFR) AF: 0.122 AC: 5081 AN: 41512

American (AMR) AF: 0.237 AC: 3624 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.203 AC: 704 AN: 3470

East Asian (EAS) AF: 0.287 AC: 1487 AN: 5174

South Asian (SAS) AF: 0.365 AC: 1755 AN: 4814

European-Finnish (FIN) AF: 0.217 AC: 2291 AN: 10572

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

European-Non Finnish (NFE) AF: 0.227 AC: 15450 AN: 67962

Other (OTH) AF: 0.202 AC: 426 AN: 2108

Alfa AF: 0.207 Hom.: 462

Bravo AF: 0.197

Asia WGS AF: 0.297 AC: 1032 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	13
DANN	Benign	0.78
PhyloP100		2.0
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: rs10892248; hg19: chr11-118501022;