NM_001144758.3:c.-22+1871G>C

Variant names:

• chr11-118609570-G-C
• rs12225399
• NM_001144758.3:c.-22+1871G>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.-22+1871G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 151,414 control chromosomes in the GnomAD database, including 10,928 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 0.37 (10928 hom., cov: 31)
• Consequence: PHLDB1 NM_001144758.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.682
• Publications: 8 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.481 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.-22+1871G>C		intron	N/A	NP_001138230.1	Q86UU1-1
	PHLDB1	NM_015157.4		c.-179+2898G>C		intron	N/A	NP_055972.1	Q86UU1-1
	PHLDB1	NM_001144759.3		c.-22+1871G>C		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.-22+1871G>C		intron	N/A	ENSP00000469820.1	Q86UU1-1
	PHLDB1	ENST00000361417.6	TSL:1	c.-179+2898G>C		intron	N/A	ENSP00000354498.2	Q86UU1-1
	PHLDB1	ENST00000860980.1		c.-978G>C		5_prime_UTR	Exon 1 of 21	ENSP00000531039.1

Frequencies

GnomAD3 genomes AF: 0.373 AC: 56467 AN: 151296 Hom.: 10918 Cov.: 31

Gnomad AFR AF: 0.487

Gnomad AMI AF: 0.286

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.363

Gnomad EAS AF: 0.284

Gnomad SAS AF: 0.418

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.382

Gnomad NFE AF: 0.343

Gnomad OTH AF: 0.378

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

GnomAD4 genome AF: 0.373 AC: 56511 AN: 151414 Hom.: 10928 Cov.: 31 AF XY: 0.371 AC XY: 27444 AN XY: 73988

African (AFR) AF: 0.487 AC: 20091 AN: 41296

American (AMR) AF: 0.271 AC: 4125 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.363 AC: 1255 AN: 3458

East Asian (EAS) AF: 0.284 AC: 1462 AN: 5142

South Asian (SAS) AF: 0.418 AC: 2006 AN: 4802

European-Finnish (FIN) AF: 0.306 AC: 3216 AN: 10518

Middle Eastern (MID) AF: 0.363 AC: 106 AN: 292

European-Non Finnish (NFE) AF: 0.343 AC: 23185 AN: 67644

Other (OTH) AF: 0.382 AC: 805 AN: 2110

Alfa AF: 0.340 Hom.: 1105

Bravo AF: 0.374

Asia WGS AF: 0.395 AC: 1369 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.0
DANN	Benign	0.50
PhyloP100		0.68
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: rs12225399; hg19: chr11-118480285; COSMIC: COSV61878044; COSMIC: COSV61878044;