rs4956990

chr5-183019-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_052909.5(PLEKHG4B):c.*696A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.416 in 152,202 control chromosomes in the GnomAD database, including 15,400 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 0.42 (15341 hom., cov: 31)
  • Exomes 𝑓: 0.52 (59 hom.)
• Consequence: PLEKHG4B NM_052909.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.263

Genes affected

PLEKHG4B (HGNC:29399): (pleckstrin homology and RhoGEF domain containing G4B) This gene encodes a large protein that contains a pleckstrin homology domain and may function as a guanine nucleotide exchange factor. [provided by RefSeq, May 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.555 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLEKHG4B	NM_052909.5	c.*696A>G		3_prime_UTR_variant	20/20	ENST00000637938.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLEKHG4B	ENST00000637938.2	c.*696A>G		3_prime_UTR_variant	20/20	5	NM_052909.5	P1
PLEKHG4B	ENST00000283426.11	c.*696A>G		3_prime_UTR_variant	18/18	1

Frequencies

GnomAD3 genomes AF: 0.416 AC: 63151 AN: 151704 Hom.: 15343 Cov.: 31

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.523

Gnomad AMR AF: 0.399

Gnomad ASJ AF: 0.462

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.513

Gnomad FIN AF: 0.499

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.560

Gnomad OTH AF: 0.412

GnomAD4 exome AF: 0.518 AC: 197 AN: 380 Hom.: 59 Cov.: 0 AF XY: 0.509 AC XY: 112 AN XY: 220

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.278

Gnomad4 SAS exome AF: 0.250

Gnomad4 FIN exome AF: 0.750

Gnomad4 NFE exome AF: 0.569

Gnomad4 OTH exome AF: 0.333

GnomAD4 genome AF: 0.416 AC: 63158 AN: 151822 Hom.: 15341 Cov.: 31 AF XY: 0.415 AC XY: 30777 AN XY: 74192

Gnomad4 AFR AF: 0.168

Gnomad4 AMR AF: 0.399

Gnomad4 ASJ AF: 0.462

Gnomad4 EAS AF: 0.270

Gnomad4 SAS AF: 0.514

Gnomad4 FIN AF: 0.499

Gnomad4 NFE AF: 0.560

Gnomad4 OTH AF: 0.411

Alfa AF: 0.514 Hom.: 21155

Bravo AF: 0.392

Asia WGS AF: 0.364 AC: 1268 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	3.1
Dann	Benign	0.60

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

Publications

LitVar

Other links and lift over

dbSNP: rs4956990; hg19: chr5-183134;