chr5-183019-A-G

Variant names:

• chr5-183019-A-G
• rs4956990
• NM_052909.5:c.*696A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052909.5. 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
	PLEKHG4B	NM_052909.5	MANE Select	c.*696A>G		3_prime_UTR	Exon 20 of 20	NP_443141.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLEKHG4B	ENST00000637938.2	TSL:5 MANE Select	c.*696A>G		3_prime_UTR	Exon 20 of 20	ENSP00000490806.1
	PLEKHG4B	ENST00000283426.11	TSL:1	c.*696A>G		3_prime_UTR	Exon 18 of 18	ENSP00000283426.6
	PLEKHG4B	ENST00000924300.1		c.*696A>G		3_prime_UTR	Exon 20 of 20	ENSP00000594359.1

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

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AF: 0.278 AC: 15 AN: 54

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.250 AC: 1 AN: 4

European-Finnish (FIN) AF: 0.750 AC: 3 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.569 AC: 173 AN: 304

Other (OTH) AF: 0.333 AC: 4 AN: 12

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

African (AFR) AF: 0.168 AC: 6944 AN: 41430

American (AMR) AF: 0.399 AC: 6074 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.462 AC: 1601 AN: 3468

East Asian (EAS) AF: 0.270 AC: 1395 AN: 5170

South Asian (SAS) AF: 0.514 AC: 2464 AN: 4798

European-Finnish (FIN) AF: 0.499 AC: 5254 AN: 10520

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.560 AC: 37997 AN: 67892

Other (OTH) AF: 0.411 AC: 865 AN: 2104

Alfa AF: 0.498 Hom.: 26337

Bravo AF: 0.392

Asia WGS AF: 0.364 AC: 1268 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.1
DANN	Benign	0.60
PhyloP100		-0.26
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: rs4956990; hg19: chr5-183134;