1-204320652-T-G

Position:

• chr1-204320652-T-G

Variant summary

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

The NM_014935.5(PLEKHA6):​c.-95+39042A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 160,772 control chromosomes in the GnomAD database, including 7,838 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 0.31 (7337 hom., cov: 32)
  • Exomes 𝑓: 0.33 (501 hom.)
• Consequence: PLEKHA6 NM_014935.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43

Genes affected

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

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLEKHA6	NM_014935.5	c.-95+39042A>C		intron_variant		ENST00000272203.8	NP_055750.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLEKHA6	ENST00000272203.8	c.-95+39042A>C		intron_variant		1	NM_014935.5	ENSP00000272203	P2
PLEKHA6	ENST00000414478.1	c.-95+39042A>C		intron_variant		5		ENSP00000402046
PLEKHA6	ENST00000564627.2	c.219-45843A>C		intron_variant		3		ENSP00000490720

Frequencies

GnomAD3 genomes AF: 0.306 AC: 46430 AN: 151966 Hom.: 7317 Cov.: 32

Gnomad AFR AF: 0.385

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.249

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.318

Gnomad FIN AF: 0.299

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.286

Gnomad OTH AF: 0.301

GnomAD4 exome AF: 0.326 AC: 2837 AN: 8690 Hom.: 501 AF XY: 0.321 AC XY: 1379 AN XY: 4300

Gnomad4 AFR exome AF: 0.451

Gnomad4 AMR exome AF: 0.0833

Gnomad4 ASJ exome AF: 0.279

Gnomad4 EAS exome AF: 0.0667

Gnomad4 SAS exome AF: 0.372

Gnomad4 NFE exome AF: 0.324

Gnomad4 OTH exome AF: 0.341

GnomAD4 genome AF: 0.306 AC: 46481 AN: 152082 Hom.: 7337 Cov.: 32 AF XY: 0.306 AC XY: 22731 AN XY: 74326

Gnomad4 AFR AF: 0.385

Gnomad4 AMR AF: 0.249

Gnomad4 ASJ AF: 0.267

Gnomad4 EAS AF: 0.139

Gnomad4 SAS AF: 0.318

Gnomad4 FIN AF: 0.299

Gnomad4 NFE AF: 0.286

Gnomad4 OTH AF: 0.298

Alfa AF: 0.287 Hom.: 12682

Bravo AF: 0.300

Asia WGS AF: 0.247 AC: 857 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.19
DANN	Benign	0.72

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: rs17333933; hg19: chr1-204289780;