rs33911350

chr1-204273710-A-Cchr1-204273710-A-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_014935.5(PLEKHA6):c.18T>G(p.Gly6=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 1,612,072 control chromosomes in the GnomAD database, including 26,090 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 0.18 (2522 hom., cov: 32)
  • Exomes 𝑓: 0.18 (23568 hom.)
• Consequence: PLEKHA6 NM_014935.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.260

Genes affected

PLEKHA6 (HGNC:17053): (pleckstrin homology domain containing A6)

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP7: Synonymous conserved (PhyloP=0.26 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLEKHA6	NM_014935.5	c.18T>G	p.Gly6=	synonymous_variant	3/23	ENST00000272203.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLEKHA6	ENST00000272203.8	c.18T>G	p.Gly6=	synonymous_variant	3/23	1	NM_014935.5	P2

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27062 AN: 151726 Hom.: 2520 Cov.: 32

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.283

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.251

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.170

GnomAD3 exomes AF: 0.193 AC: 48375 AN: 251220 Hom.: 4937 AF XY: 0.190 AC XY: 25752 AN XY: 135776

Gnomad AFR exome AF: 0.140

Gnomad AMR exome AF: 0.243

Gnomad ASJ exome AF: 0.136

Gnomad EAS exome AF: 0.274

Gnomad SAS exome AF: 0.182

Gnomad FIN exome AF: 0.245

Gnomad NFE exome AF: 0.171

Gnomad OTH exome AF: 0.170

GnomAD4 exome AF: 0.176 AC: 256808 AN: 1460228 Hom.: 23568 Cov.: 31 AF XY: 0.176 AC XY: 127830 AN XY: 726526

Gnomad4 AFR exome AF: 0.133

Gnomad4 AMR exome AF: 0.238

Gnomad4 ASJ exome AF: 0.139

Gnomad4 EAS exome AF: 0.259

Gnomad4 SAS exome AF: 0.182

Gnomad4 FIN exome AF: 0.241

Gnomad4 NFE exome AF: 0.169

Gnomad4 OTH exome AF: 0.179

GnomAD4 genome AF: 0.178 AC: 27079 AN: 151844 Hom.: 2522 Cov.: 32 AF XY: 0.184 AC XY: 13659 AN XY: 74200

Gnomad4 AFR AF: 0.141

Gnomad4 AMR AF: 0.212

Gnomad4 ASJ AF: 0.141

Gnomad4 EAS AF: 0.283

Gnomad4 SAS AF: 0.197

Gnomad4 FIN AF: 0.251

Gnomad4 NFE AF: 0.176

Gnomad4 OTH AF: 0.170

Alfa AF: 0.161 Hom.: 1543

Bravo AF: 0.172

Asia WGS AF: 0.273 AC: 950 AN: 3478

EpiCase AF: 0.165

EpiControl AF: 0.166

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
Cadd	Benign	12
Dann	Benign	0.77

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: rs33911350; hg19: chr1-204242838; COSMIC: COSV55331667; COSMIC: COSV55331667;