chr3-111919285-A-C

Variant names:

• chr3-111919285-A-C
• rs951660
• NM_001134438.2:c.1863+70A>C

Variant summary

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

The NM_001134438.2(PHLDB2):​c.1863+70A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.881 in 1,531,756 control chromosomes in the GnomAD database, including 595,875 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 0.86 (56961 hom., cov: 32)
  • Exomes 𝑓: 0.88 (538914 hom.)
• Consequence: PHLDB2 NM_001134438.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.556
• Publications: 8 publications found

Genes affected

PHLDB2 (HGNC:29573): (pleckstrin homology like domain family B member 2) Enables cadherin binding activity. Involved in several processes, including negative regulation of focal adhesion assembly; regulation of cytoskeleton organization; and regulation of embryonic development. Located in several cellular components, including basal cortex; cell leading edge; and intermediate filament cytoskeleton. Colocalizes with focal adhesion. [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 (EAS) allele frequency at 95% confidence interval = 0.884 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHLDB2	NM_001134438.2	c.1863+70A>C		intron_variant	Intron 4 of 17	ENST00000431670.7	NP_001127910.1
PHLDB2	NM_001134439.2	c.1863+70A>C		intron_variant	Intron 4 of 17		NP_001127911.1
PHLDB2	NM_001134437.2	c.1944+70A>C		intron_variant	Intron 5 of 17		NP_001127909.1
PHLDB2	NM_145753.2	c.1863+70A>C		intron_variant	Intron 4 of 16		NP_665696.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHLDB2	ENST00000431670.7	c.1863+70A>C		intron_variant	Intron 4 of 17	1	NM_001134438.2	ENSP00000405405.2

Frequencies

GnomAD3 genomes AF: 0.864 AC: 131388 AN: 152098 Hom.: 56944 Cov.: 32

Gnomad AFR AF: 0.802

Gnomad AMI AF: 0.930

Gnomad AMR AF: 0.876

Gnomad ASJ AF: 0.967

Gnomad EAS AF: 0.899

Gnomad SAS AF: 0.759

Gnomad FIN AF: 0.909

Gnomad MID AF: 0.930

Gnomad NFE AF: 0.890

Gnomad OTH AF: 0.874

GnomAD4 exome AF: 0.883 AC: 1217847 AN: 1379540 Hom.: 538914 AF XY: 0.880 AC XY: 607308 AN XY: 690054

African (AFR) AF: 0.798 AC: 25186 AN: 31554

American (AMR) AF: 0.881 AC: 38678 AN: 43888

Ashkenazi Jewish (ASJ) AF: 0.962 AC: 24317 AN: 25276

East Asian (EAS) AF: 0.935 AC: 36652 AN: 39182

South Asian (SAS) AF: 0.770 AC: 63758 AN: 82812

European-Finnish (FIN) AF: 0.902 AC: 47475 AN: 52624

Middle Eastern (MID) AF: 0.905 AC: 4338 AN: 4796

European-Non Finnish (NFE) AF: 0.890 AC: 926746 AN: 1041740

Other (OTH) AF: 0.879 AC: 50697 AN: 57668

GnomAD4 genome AF: 0.864 AC: 131452 AN: 152216 Hom.: 56961 Cov.: 32 AF XY: 0.865 AC XY: 64357 AN XY: 74418

African (AFR) AF: 0.801 AC: 33232 AN: 41484

American (AMR) AF: 0.875 AC: 13392 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.967 AC: 3356 AN: 3472

East Asian (EAS) AF: 0.900 AC: 4666 AN: 5186

South Asian (SAS) AF: 0.759 AC: 3663 AN: 4828

European-Finnish (FIN) AF: 0.909 AC: 9636 AN: 10596

Middle Eastern (MID) AF: 0.932 AC: 274 AN: 294

European-Non Finnish (NFE) AF: 0.890 AC: 60546 AN: 68032

Other (OTH) AF: 0.870 AC: 1839 AN: 2114

Alfa AF: 0.878 Hom.: 24181

Bravo AF: 0.860

Asia WGS AF: 0.790 AC: 2746 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.9
DANN	Benign	0.50
PhyloP100		-0.56
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: rs951660; hg19: chr3-111638132; COSMIC: COSV67309266; COSMIC: COSV67309266;