chr5-169787-T-C

Position:

• chr5-169787-T-C

Variant summary

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

The NM_052909.5(PLEKHG4B):​c.3729+195T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.662 in 152,190 control chromosomes in the GnomAD database, including 34,045 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 0.66 (34045 hom., cov: 34)
• Consequence: PLEKHG4B NM_052909.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.588

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]

PLEKHG4B (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.717 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLEKHG4B	NM_052909.5	c.3729+195T>C		intron_variant		ENST00000637938.2	NP_443141.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLEKHG4B	ENST00000637938.2	c.3729+195T>C		intron_variant		5	NM_052909.5	ENSP00000490806.1
PLEKHG4B	ENST00000283426.11	c.2661+195T>C		intron_variant		1		ENSP00000283426.6
PLEKHG4B	ENST00000504041.1	n.540+195T>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.662 AC: 100674 AN: 152072 Hom.: 34021 Cov.: 34

Gnomad AFR AF: 0.648

Gnomad AMI AF: 0.822

Gnomad AMR AF: 0.567

Gnomad ASJ AF: 0.619

Gnomad EAS AF: 0.279

Gnomad SAS AF: 0.619

Gnomad FIN AF: 0.681

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.722

Gnomad OTH AF: 0.641

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

GnomAD4 genome AF: 0.662 AC: 100756 AN: 152190 Hom.: 34045 Cov.: 34 AF XY: 0.656 AC XY: 48796 AN XY: 74418

Gnomad4 AFR AF: 0.648

Gnomad4 AMR AF: 0.567

Gnomad4 ASJ AF: 0.619

Gnomad4 EAS AF: 0.280

Gnomad4 SAS AF: 0.620

Gnomad4 FIN AF: 0.681

Gnomad4 NFE AF: 0.722

Gnomad4 OTH AF: 0.639

Alfa AF: 0.696 Hom.: 22853

Bravo AF: 0.648

Asia WGS AF: 0.440 AC: 1534 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	1.3
DANN	Benign	0.30

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: rs1108867; hg19: chr5-169902; COSMIC: COSV52055222;