chr11-118615352-T-C

Variant names:

• chr11-118615352-T-C
• rs11603023
• NM_001144758.3:c.184+670T>C

Variant summary

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

The NM_001144758.3(PHLDB1):​c.184+670T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.575 in 151,808 control chromosomes in the GnomAD database, including 25,308 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 0.58 (25308 hom., cov: 31)
• Consequence: PHLDB1 NM_001144758.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.541
• Publications: 58 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 (EAS) allele frequency at 95% confidence interval = 0.701 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.184+670T>C		intron	N/A	NP_001138230.1
	PHLDB1	NM_015157.4		c.184+670T>C		intron	N/A	NP_055972.1
	PHLDB1	NM_001144759.3		c.184+670T>C		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.184+670T>C		intron	N/A	ENSP00000469820.1
	PHLDB1	ENST00000361417.6	TSL:1	c.184+670T>C		intron	N/A	ENSP00000354498.2
	PHLDB1	ENST00000356063.9	TSL:2	c.184+670T>C		intron	N/A	ENSP00000348359.5

Frequencies

GnomAD3 genomes AF: 0.575 AC: 87274 AN: 151688 Hom.: 25275 Cov.: 31

Gnomad AFR AF: 0.506

Gnomad AMI AF: 0.661

Gnomad AMR AF: 0.693

Gnomad ASJ AF: 0.587

Gnomad EAS AF: 0.720

Gnomad SAS AF: 0.588

Gnomad FIN AF: 0.576

Gnomad MID AF: 0.615

Gnomad NFE AF: 0.578

Gnomad OTH AF: 0.572

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

GnomAD4 genome AF: 0.575 AC: 87360 AN: 151808 Hom.: 25308 Cov.: 31 AF XY: 0.578 AC XY: 42888 AN XY: 74174

African (AFR) AF: 0.506 AC: 20913 AN: 41354

American (AMR) AF: 0.694 AC: 10595 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.587 AC: 2036 AN: 3468

East Asian (EAS) AF: 0.720 AC: 3709 AN: 5148

South Asian (SAS) AF: 0.588 AC: 2824 AN: 4804

European-Finnish (FIN) AF: 0.576 AC: 6063 AN: 10534

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.578 AC: 39227 AN: 67916

Other (OTH) AF: 0.572 AC: 1208 AN: 2112

Alfa AF: 0.579 Hom.: 110798

Bravo AF: 0.582

Asia WGS AF: 0.615 AC: 2138 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.43
DANN	Benign	0.71
PhyloP100		-0.54
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: rs11603023; hg19: chr11-118486067;