rs494560

Variant names:

• chr11-118650844-A-G
• rs494560
• NM_001144758.3:c.3874+297A>G

Variant summary

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

The NM_001144758.3(PHLDB1):​c.3874+297A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.58 in 402,654 control chromosomes in the GnomAD database, including 68,777 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 0.57 (25214 hom., cov: 32)
  • Exomes 𝑓: 0.58 (43563 hom.)
• Consequence: PHLDB1 NM_001144758.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.483
• Publications: 14 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 (EAS) allele frequency at 95% confidence interval = 0.7 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHLDB1	NM_001144758.3	c.3874+297A>G		intron_variant	Intron 20 of 22	ENST00000600882.6	NP_001138230.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHLDB1	ENST00000600882.6	c.3874+297A>G		intron_variant	Intron 20 of 22	1	NM_001144758.3	ENSP00000469820.1

Frequencies

GnomAD3 genomes AF: 0.574 AC: 87125 AN: 151854 Hom.: 25183 Cov.: 32

Gnomad AFR AF: 0.504

Gnomad AMI AF: 0.657

Gnomad AMR AF: 0.692

Gnomad ASJ AF: 0.586

Gnomad EAS AF: 0.719

Gnomad SAS AF: 0.584

Gnomad FIN AF: 0.574

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.576

Gnomad OTH AF: 0.570

GnomAD4 exome AF: 0.585 AC: 146526 AN: 250684 Hom.: 43563 Cov.: 0 AF XY: 0.583 AC XY: 76437 AN XY: 131172

African (AFR) AF: 0.502 AC: 4009 AN: 7988

American (AMR) AF: 0.730 AC: 7222 AN: 9898

Ashkenazi Jewish (ASJ) AF: 0.578 AC: 4544 AN: 7868

East Asian (EAS) AF: 0.732 AC: 11010 AN: 15040

South Asian (SAS) AF: 0.558 AC: 15785 AN: 28308

European-Finnish (FIN) AF: 0.577 AC: 8135 AN: 14108

Middle Eastern (MID) AF: 0.584 AC: 660 AN: 1130

European-Non Finnish (NFE) AF: 0.571 AC: 86742 AN: 151780

Other (OTH) AF: 0.578 AC: 8419 AN: 14564

GnomAD4 genome AF: 0.574 AC: 87209 AN: 151970 Hom.: 25214 Cov.: 32 AF XY: 0.576 AC XY: 42786 AN XY: 74274

African (AFR) AF: 0.504 AC: 20853 AN: 41402

American (AMR) AF: 0.693 AC: 10588 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.586 AC: 2035 AN: 3470

East Asian (EAS) AF: 0.719 AC: 3720 AN: 5172

South Asian (SAS) AF: 0.584 AC: 2813 AN: 4814

European-Finnish (FIN) AF: 0.574 AC: 6059 AN: 10550

Middle Eastern (MID) AF: 0.630 AC: 184 AN: 292

European-Non Finnish (NFE) AF: 0.576 AC: 39156 AN: 67964

Other (OTH) AF: 0.570 AC: 1203 AN: 2110

Alfa AF: 0.578 Hom.: 14203

Bravo AF: 0.581

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.86
PhyloP100		-0.48

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs494560; hg19: chr11-118521549;