chr11-118628678-C-G

Variant names:

• chr11-118628678-C-G
• rs2236661
• NM_001144758.3:c.1827+28C>G

Variant summary

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

The NM_015157.4(PHLDB1):​c.1827+28C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 1,581,766 control chromosomes in the GnomAD database, including 41,723 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 (3322 hom., cov: 33)
  • Exomes 𝑓: 0.23 (38401 hom.)
• Consequence: PHLDB1 NM_015157.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.527
• Publications: 17 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.345 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015157.4. 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.1827+28C>G		intron	N/A	NP_001138230.1
	PHLDB1	NM_015157.4		c.1827+28C>G		intron	N/A	NP_055972.1
	PHLDB1	NM_001144759.3		c.1827+28C>G		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.1827+28C>G		intron	N/A	ENSP00000469820.1
	PHLDB1	ENST00000361417.6	TSL:1	c.1827+28C>G		intron	N/A	ENSP00000354498.2
	PHLDB1	ENST00000532517.5	TSL:1	n.1721+28C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30825 AN: 152118 Hom.: 3319 Cov.: 33

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.247

Gnomad SAS AF: 0.357

Gnomad FIN AF: 0.217

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.198

GnomAD2 exomes AF: 0.237 AC: 45904 AN: 193578 AF XY: 0.245

Gnomad AFR exome AF: 0.119

Gnomad AMR exome AF: 0.217

Gnomad ASJ exome AF: 0.205

Gnomad EAS exome AF: 0.252

Gnomad FIN exome AF: 0.226

Gnomad NFE exome AF: 0.227

Gnomad OTH exome AF: 0.234

GnomAD4 exome AF: 0.229 AC: 326927 AN: 1429530 Hom.: 38401 Cov.: 32 AF XY: 0.232 AC XY: 164925 AN XY: 709602

African (AFR) AF: 0.117 AC: 3792 AN: 32428

American (AMR) AF: 0.215 AC: 8425 AN: 39110

Ashkenazi Jewish (ASJ) AF: 0.203 AC: 5175 AN: 25438

East Asian (EAS) AF: 0.222 AC: 8546 AN: 38510

South Asian (SAS) AF: 0.339 AC: 28139 AN: 82960

European-Finnish (FIN) AF: 0.221 AC: 10534 AN: 47590

Middle Eastern (MID) AF: 0.222 AC: 1235 AN: 5562

European-Non Finnish (NFE) AF: 0.225 AC: 247442 AN: 1098728

Other (OTH) AF: 0.230 AC: 13639 AN: 59204

GnomAD4 genome AF: 0.203 AC: 30834 AN: 152236 Hom.: 3322 Cov.: 33 AF XY: 0.206 AC XY: 15348 AN XY: 74424

African (AFR) AF: 0.123 AC: 5108 AN: 41560

American (AMR) AF: 0.236 AC: 3617 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.201 AC: 697 AN: 3470

East Asian (EAS) AF: 0.247 AC: 1274 AN: 5162

South Asian (SAS) AF: 0.359 AC: 1731 AN: 4826

European-Finnish (FIN) AF: 0.217 AC: 2296 AN: 10600

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

European-Non Finnish (NFE) AF: 0.227 AC: 15465 AN: 67994

Other (OTH) AF: 0.200 AC: 422 AN: 2114

Alfa AF: 0.210 Hom.: 656

Bravo AF: 0.195

Asia WGS AF: 0.273 AC: 947 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.8
DANN	Benign	0.49
PhyloP100		-0.53
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2236661; hg19: chr11-118499394; COSMIC: COSV61877152; COSMIC: COSV61877152;